Ovarian carcinomas are thought to arise from cells of the ovarian surface epithelium by mechanisms that are poorly understood. Molecules associated with neoplasia are potentially immunogenic, but few ovarian tumor antigens have been identified. Because ovarian carcinomas can elicit humoral responses in patients, we searched for novel tumor antigens by immunoscreening a cDNA expression library with ovarian cancer patient serum. Seven clones corresponding to the homeobox gene HOXB7 were isolated. ELISAs using purified recombinant HOXB7 protein revealed significant serologic reactivity to HOXB7 in 13 of 39 ovarian cancer patients and in only one of 29 healthy women (P < 0.0001). Ovarian carcinomas were found to express HOXB7 at markedly higher levels than normal ovarian surface epithelium, suggesting that immunogenicity of HOXB7 in patients could be associated with its elevated expression in ovarian carcinomas. Overexpression of HOXB7 in immortalized normal ovarian surface epithelial cells dramatically enhanced cellular proliferation. Furthermore, HOXB7 overexpression increased intracellular accumulation and secretion of basic fibroblast growth factor, a potent angiogenic and mitogenic factor. These results reveal HOXB7 as a tumor antigen whose up-regulated expression could play a significant role in promoting growth and development of ovarian carcinomas.
Heilaohu, the roots of Kadsura coccinea, has a long history of use in Tujia ethnomedicine for the treatment of rheumatoid arthritis and gastroenteric disorders, and a lot of work has been done in order to know the material basis of its pharmacological activities. The chemical investigation led to the isolation and characterization of three new (1–3) and twenty known (4–23) lignans. Three new heilaohulignans A-C (1–3) and seventeen known (4–20) lignans possessed dibenzocyclooctadiene skeletons. Similarly, one was a diarylbutane (21) and two were spirobenzofuranoid dibenzocyclooctadiene (22–23) lignans. Among the known compounds, 4–5, 7, 13–15 and 17–22 were isolated from this species for the first time. The structures were established, using IR, UV, MS and NMR data. The absolute configurations of the new compounds were determined by circular dichroism (CD) spectra. The isolated lignans were further evaluated for their cytotoxicity and antioxidant activities. Compound 3 demonstrated strong cytotoxic activity with an IC50 value of 9.92 µM, compounds 9 and 13 revealed weak cytotoxicity with IC50 values of 21.72 µM and 18.72 µM, respectively in the HepG-2 human liver cancer cell line. Compound 3 also showed weak cytotoxicity against the BGC-823 human gastric cancer cell line and the HCT-116 human colon cancer cell line with IC50 values of 16.75 µM and 16.59 µM, respectively. A chemiluminescence assay for antioxidant status of isolated compounds implied compounds 11 and 20, which showed weak activity with IC50 values of 25.56 µM and 21.20 µM, respectively.
Glutathione (GSH) levels are closely related to the homeostasis
of redox state which directly affects human disease occurrence by
regulating cell apoptosis. Hence, real-time monitoring of dynamic
changes in intracellular GSH levels is urgently needed for disease
early diagnosis and evaluation of therapy efficiency. In this study,
an endogenous cysteine (Cys)-assisted detection system based on GSH@AgNCs
and reduced graphene oxide (rGO) with high sensitivity and specificity
was developed for GSH detection. Compared with GSH, GSH@AgNCs with
weaker affinity and bonding force was quite easier to extrude from
the rGO surface when competing against GSH, leading to the obvious
change in fluorescence signal. This phenomenon was termed as “a
crowding out effect”. Furthermore, the presence of Cys can
improve GSH assay sensitivity by enhancing the quenching efficiency
of rGO on the GSH@AgNCs. In vitro assay indicated that the efficiency
of fluorescence recovery was positively related with GSH concentration
in the range from 0 to 10 mM. In addition, the method was employed
for real-time monitoring of the dynamic changes in GSH levels regulated
by natural drugs. The imaging results showed that the natural compound 3 (C3) can downregulate GSH levels in HepG2 cells, which was
accompanied by reactive oxygen species (ROS) release and apoptosis
induction. Finally, the method was used to monitor the change of GSH
levels in serum samples with chronic hepatitis B (CHB) infection.
The results demonstrated that the occurrence and development of CHB
may be positively correlated with GSH levels to some extent. Overall,
the above results demonstrate the potential application of this new
nanosystem in anticancer natural drug screening and clinical assay
regarding GSH levels.
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