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The genus Sechium P. Br. (Cucurbitaceae) includes ten species, two of which are edible. The inedible genotypes are in a fragile ecological niche, since they are not used by rural inhabitants. A rescue and genetic crossing program was designed to identify uses that favor their conservation due to their content of bioactive secondary metabolites (Sm) for health. Fruits of S. compositum (wild type), hybrid H-D Victor (inedible), and S. edule var. nigrum spinosum (edible) were evaluated by extraction methods such as juice and oven drying to determine the yields of Sm, with in vivo evaluations of liver damage. The dried biomass (40 °C) extracted with ethanolic and methanolic procedures showed lower Sm content than the juice (fresh biomass). More than 90% of phenolic acids and cucurbitacins in the extracts were degraded, possibly due to the drying time (oven). Biological activity showed that nigrum spinosum and HD-Victor have fewer toxic metabolites than S. compositum. The hybrid H-D Victor is of reduced cytotoxicity, showing the advantages of hybridization with wild types. Phytochemical and biological activity characterization may contribute to the conservation of genotypes and become a source of bioactive natural products. [ABSTRACT FROM AUTHOR]

There are hereditary mutations that predispose individuals to cancer development, such as pathogenic variants in the germ line of the tumor protein 53 (TP53) suppressor gene. This leads to a rare condition known as Li–Fraumeni syndrome (LFS), characterized by a high risk of developing multiple cancers throughout life by the precancerous niche that promotes the tumor microenvironment. LFS presents a significant challenge due to its limited therapeutic and chemoprophylactic options. Recently, protocols involving metformin as a prophylactic medication have been developed to target precancerous niches. However, this approach is still in the clinical phase, and no established therapeutic regimen is available. Therefore, new alternatives are needed to impact this disease effectively. Novel studies suggest that Sechium extract, rich in polyphenols, exhibits chemoprophylactic, antineoplastic, anti-inflammatory, and antioxidant activities, all involved in the tumor microenvironment of LFS. However, the specific role of Sechium extract in preventing recurrent neoplastic development in LFS remains unclear. We conducted this research through a case report of an LFS-diagnosed patient who has experienced multiple malignancies and cutaneous neoformations. This patient received a chemoprophylactic supplementation based on Sechium H387 07 extract over 11 years without reporting new primary malignancy events or recurrences, as evidenced by laboratory and positron emission tomography/computed tomography (PET/CT) studies. An extensive literature review on the disease, precancerous niche, tumor microenvironment, and potential mechanisms of Sechium H387 07 extract components was conducted to explain cancer absence in LFS. This review promotes the research and use of polyphenols as powerful chemoprophylactic agents to prevent and treat proliferative diseases like LFS. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a hematological neoplasm of rapid and progressive onset, and is the most common form of leukemia in adults. Chemoresistance to conventional treatments such as cytarabine (Ara-C) and daunorubicin is a main cause of relapse, recurrence, metastasis, and high mortality in AML patients. It is known that sodium caseinate (SC), a salt derived from casein, a milk protein, inhibits growth and induces apoptosis in acute myeloid leukemia cells but not in normal hematopoietic cells. However, it is unknown whether SC retains its antileukemic effect in cytarabine-resistant AML cell lines. Objective: To evaluate the antineoplastic effect of SC in cytarabine-resistant leukemia models. Methods: The SC inhibits the growth and induces apoptosis in parental WEHI-3 AML cells. Here, we generated two cytarabine-resistant sublines, WEHI-CR25 and WEHI-CR50, which exhibit 6- and 16-fold increased resistance to cytarabine, respectively, compared to the parental WEHI-3 cells. Thus, these sublines mimic a chemoresistant model. Results: We demonstrate that WEHI-CR25 and WEHI-CR50 cells retain sensitivity to SC, similar to parental WEHI-3 cells. This sensitivity results in inhibited cell proliferation, induced apoptosis, and increased expression of ENT1 and dCK, molecules involved in the entry and metabolism of Ara-C, while decreasing MDR1 expression. Additionally, we observed that SC prolonged the survival of WEHI-CR50 tumor-bearing mice, despite their resistance to Ara-C. Conclusion: This is the first evidence that SC, a milk protein, may inhibit proliferation and induce apoptosis in cytarabine-resistant cells. [ABSTRACT FROM AUTHOR]

Microencapsulation is a technique used in pharmaceuticals as an administration vehicle. Encapsulating secondary metabolites for therapeutic purposes has been promoted recently. Microencapsulation based on chitosan was developed for the methanol extract of cv. Perla negra (S. edule (Jacq.) Sw.) (Cucurbitaceae) fruits to evaluate its viability as an administration vehicle and to assess the possible negative interaction between the extract and chitosan. Microencapsulation was performed by coacervation, implementing a method with constant sonication. The microparticles obtained were registered by means of Scanning Electron Microscopy. The presence of the bioactive in aqueous medium was recorded for release tests, measuring with spectrophotometry its concentration as a function of time. The assessment of the biological effect of the microencapsulated extract was done on the HeLa cell line and control cells (lymphocytes). Microspheres with an average size of 20 µm and a loading capacity of 98% were obtained. The highest concentration of released extract was 24 µg mL−1 at 23 h. The mainly chitosan-based microspheres did not affect the antiproliferative activity of the extract of cv. Perla negra and proved to be a potential vehicle for its therapeutic administration. The empty microspheres made with chitosan also showed to have an antiproliferative effect, and those loaded with extract showed cellular inhibition (statistical IC50) of 8 µg mL−1 without affecting the lymphocytes. Chitosan does not interfere with the biological activity of the metabolites incorporated into the microspheres since they retain their inhibitory activity on proliferation in tumor cells, thus constituting a potential vehicle for the therapeutic administration of fruit extract. [ABSTRACT FROM AUTHOR]

Abstract Background The presence of IgG antibodies to HPV-16 L1-virus like particles (VLPs) in serum has been reported as a result of persistent exposure to the virus and as a marker of disease progression. However, detection of VLP-specific antibodies in sera does not always indicate a malignant lesion as positive results may also be due to a nonmalignant viral infection. Furthermore, malignant lesions are associated with an increased antibody titer for E6 and E7 proteins. The aim of this study was to develop an ELISA using a novel chimeric virus-like particle (cVLP) encoding an L1 protein fused with a string of HPV-16 E6 and E7 seroreactive epitopes to its C-terminus to be used for detection of HPV-16 specific antibodies in patients with cervical intraepithelial lesion grade 1 (CIN 1). Results The sera of 30 patients with CIN 1 who also tested positive for HPV-16 DNA and of 30 age-matched normal donors negative for HPV infection were tested for the presence of IgG antibodies specific for either VLP-L1 (HPV-16 L1), gVLP (derived from Gardasil), or cVLP by ELISA. The cVLP-reactive sera yielded two distinct groups of results: (H) reactivity levels that presented very strong cVLP-specific titers, and (L) reactivity levels with significantly lower titers similar to those obtained with VLP-L1 and gVLP antigens. Additionally, the sera that presented the higher cVLP titers closely matched those that had significantly stronger reactivity to E6 and E7 epitopes. Interestingly, the samples with the highest titers corresponded to patients with the higher numbers of sexual partners and pregnancies. On the other hand only 4 out of the 12 sera that harbored antibodies with VLP neutralizing ability corresponded to the group with high cVLP antibody titers. Conclusion We report for the first time that chimeric particles containing HPV-16 L1 protein fused with E6 and E7 seroreactive epitopes enable much better detection of IgG antibodies in the sera of CIN 1 patients positive for HPV-16 infection than those obtained with VLPs containing only the HPV-16 L1 protein. We also found that the sera with higher cVLP antibody titers corresponded to patients with more sexual partners and pregnancies, and not always with to those with a high neutralizing activity. This novel assay could help in the development of a tool to evaluate cervical cancer risk.