Lacking a satisfactory screening test, ovarian cancer is frequently diagnosed at a late stage, leading to poor patient outcomes. This study investigated the diagnostic value of circulating tumor cells (CTCs) in peripheral blood from patients with suspected ovarian tumors. Sixty-one women suspected of having an ovarian mass were prospectively enrolled in this study. CTCs were identified and counted using microfluidic isolation and immunofluorescent staining of CD45, HE4, and epithelial and mesenchymal (E&M) markers (epithelial cell adhesion molecule, cytokeratins, and vimentin). Thirty (49%) of the patients were diagnosed with ovarian cancer. DAPI+/E&M+/CD45-/HE4+ CTC counts were higher in these patients than in patients with benign tumors (p = 0.016). The receiver operating characteristic (ROC) curve showed that the sensitivity of CTCs was 73.3%, which was superior to that of CA125 (56.7%). In patients with elevated CA125 levels (≥35 U/ml), CTC counts still showed good specificity (86.7%). Our findings suggest the DAPI+/E&M+/CD45-/HE4+ CTC count is a useful diagnostic indicator in patients with suspected ovarian cancer.
Background: To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. Methods: The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. Results: In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs.Conclusions: COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.
More than 2 billion people worldwide are under threat of nutritional deficiency. Thus, an in-depth comprehension of the nutritional composition of staple crops and popular fruits is essential for health. Herein, we performed LC-MS-based non-targeted and targeted metabolome analyses with crops (including wheat, rice, and corn) and fruits (including grape, banana, and mango). We detected a total of 2631 compounds by using non-targeted strategy and identified more than 260 nutrients. Our work discovered species-dependent accumulation of common present nutrients in crops and fruits. Although rice and wheat lack vitamins and amino acids, sweet corn was rich in most amino acids and vitamins. Among the three fruits, mango had more vitamins and amino acids than grape and banana. Grape and banana provided sufficient 5-methyltetrahydrofolate and vitamin B6, respectively. Moreover, rice and grape had a high content of flavonoids. In addition, the three crops contained more lipids than fruits. Furthermore, we also identified species-specific metabolites. The crops yielded 11 specific metabolites, including flavonoids, lipids, and others. Meanwhile, most fruit-specific nutrients were flavonoids. Our work discovered the complementary pattern of essential nutrients in crops and fruits, which provides metabolomic evidence for a healthy diet.
Objective: We aimed to evaluate the ability of the fluorescent monoclonal antibody probe COC183B2-Cy7 (Cy7-conjugated COC183B2 antibody) to detect tiny metastatic lesions of ovarian cancer and thus guide precise tumor resection. Methods: The expression of the tumor-associated antigen OC183B2 in lymph nodes and SKOV3-Luc cells was detected using immunohistochemistry and immunofluorescence. A subcutaneous mouse tumor model and an intraperitoneal ovarian cancer metastasis model were constructed using SKOV3-Luc cells. Near-infrared fluorescence (NIRF) imaging was performed to determine the imaging parameters and evaluate the ability of COC183B2-Cy7 to detect tiny metastatic lesions. Results: OC183B2 was expressed in metastatic lymph nodes and SKOV3-Luc cells. NIRF imaging of the subcutaneous mouse tumor model showed that the tumor background ratio was significantly higher in the COC183B2-Cy7 group than in the control group at different time points postinjection. Biodistribution study showed that COC183B2-Cy7 did not accumulate in other organs. COC183B2-Cy7 can detect tiny metastatic lesions of ovarian cancer. The smallest intraperitoneal metastatic tumor detected by COC183B2-Cy7 was approximately 1 mm. Conclusions: COC183B2-Cy7 probe has relatively high specificity and sensitivity. Our study suggests that COC183B2-Cy7 probe is a promising diagnostic tool for the complete and accurate resection of malignant lesions in fluorescence-guided surgery.
ObjectiveTo evaluate the imaging potential of a novel near-infrared (NIR) probe conjugated to COC183B2 monoclonal antibodies (MAb) in ovarian cancer (OC).MethodsThe expression of OC183B2 antigen in OC was determined by immunohistochemical (IHC) staining using tissue microarrays with the H-score system and immunofluorescence (IF) staining of tumor cell lines. Imaging probes with the NIR fluorescent dye cyanine 7 (Cy7) conjugated to COC183B2 Mab were chemically engineered. OC183B2-positive human OC cells (SKOV3-Luc) were injected subcutaneously into BALB/c nude mice. Bioluminescent imaging (BLI) was performed to detect tumor location and growth. COC183B2-Cy7 at 1.1, 3.3, 10, or 30 μg were used for in vivo fluorescence imaging, and phosphate-buffered saline (PBS), free Cy7 dye and mouse isotype immunoglobulin G (IgG)-Cy7 (delivered at the same doses as COC183B2-Cy7) were used as controls. ResultsThe expression of OC183B2 with a high H-score was more prevalent in OC tissue than fallopian tube (FT) tissue. Among 417 OC patients, the expression of OC183B2 was significantly correlated with the histological subtype, histological grade, residual tumor size, relapse state and survival status. IF staining demonstrated that COC183B2 specifically expressed in SKOV3 cells but not HeLa cells. In vivo NIR fluorescence imaging indicated that COC183B2-Cy7 was mainly distributed in the xenograft and liver with optimal tumor-to-background (T/B) ratios in the xenograft at 30 μg dose. The highest fluorescent signals in the tumor were observed at 96 h post-injection (hpi). Ex vivo fluorescence imaging revealed the fluorescent signals mainly from the tumor and liver. IHC analysis confirmed that xenografts were OC183B2 positive. ConclusionsCOC183B2 is a good candidate for NIR fluorescence imaging and imaging-guided surgery in OC.
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