Autologous PRP therapy for thin endometrium: A self-controlled case series study across menstrual cycles.

OBJECTIVES: Thin endometrium (TE) compromises endometrial receptivity, often leading to implantation failure and lower clinical pregnancy rates. As autologous platelet-rich plasma (PRP) emerges as a potential remedy, the present study focused on its therapeutic effects on TE in infertile women who underwent frozen embryo transfer. STUDY DESIGN: Patients with TE who underwent frozen embryo transfer treatment in our hospital were included. To diminish individual variability, a self-controlled series approach was used. Two menstrual study cycles were arranged for each participant before the actual embryo transfer cycle; PRP treatment was conducted in the second cycle. Key metrics analyzed included endometrial thickness and the expression of specific endometrial biomarkers including HOXA-10, Ki67, and αvß3 integrin. Transvaginal ultrasound was employed to measure endometrial thickness on Days 11 and 14, and an endometrial biopsy was conducted on progesterone Day 5 of the first two cycles. Pregnancy outcomes were observed after the embryo transfer cycle. RESULTS: PRP treatment significantly increased the median endometrial thickness, from 5.8 mm to 6.5 mm (P = 0.0066). Additionally, PRP treatment resulted in a statistically significant increase in the H-score for all endometrial markers. Importantly, during the subsequent embryo transfer cycle with PRP treatment, two patients successfully achieved pregnancies, both culminating in live births. CONCLUSIONS: These findings emphasize the potential of PRP in improving endometrial conditions, especially for individuals grappling with thin endometrium issues, as underscored by this self-comparison methodology.

An integrated microfluidic system for rapid, automatic and high-throughput staining of clinical tissue samples for diagnosis of ovarian cancer.

Accurate cancer diagnostic methods are of urgent need. Since traditional immunohistochemistry (IHC)-based approaches, while reliable, are labor-intensive and require well-trained technicians, we developed an integrated microfluidic platform capable of labeling ovarian cancer biomarkers (i.e. aptamer) within formalin-fixed, paraffin embedded tissues via molecular probes. Both aptamer-based 1) fluorescent staining and 2) IHC staining of clinical tissue samples could be automated in the microfluidic system in only 2-3 h (40-50% faster than conventional approaches) with <0.5 mL of reagents, signifying that this device could serve as a promising diagnostic tool for ovarian cancer.

An automated microfluidic system for selection of aptamer probes against ovarian cancer tissues.

Because of the difficulty of treatment in its latest stages, cancer is among the leading causes of death worldwide. Therefore, high-affinity and specificity biomarkers are still in demand for many cancer types, and the utility of aptamers to serve in this regard has been explored recently. Although a process known as "systematic evolution of ligands by exponential enrichment" (SELEX) has been used to generate aptamer-based cancer biomarkers, this approach is complicated, time-consuming, and labor-intensive. An automated microfluidic system was consequently developed herein to screen ovarian cancer-specific aptamers via on-chip SELEX with clinical cancer tissue samples. The integrated microfluidic system consisted of an integrated microfluidic chip, a temperature control module equipped with 12 thermoelectric coolers, and a flow control module for controlling 36 electromagnetic valves such that the entire, tissue-based SELEX process could be fully automated and carried out within 15 h. Highly specific ovarian cancer aptamers with high affinity (dissociation constant of 129 nM) to their cellular targets were screened with this system. Given the comparable specificity to their much more expensive antibody counterparts, these aptamers, when used in conjunction with the developed microfluidic system, may be used to diagnose ovarian cancer in its earliest stages.

Microfluidic platforms for rapid screening of cancer affinity reagents by using tissue samples.

Cancer is the most serious disease worldwide, and ovarian cancer (OvCa) is the second most common type of gynecological cancer. There is consequently an urgent need for early-stage detection of OvCa, which requires affinity reagent biomarkers for OvCa. Systematic evolution of ligands by exponential enrichment (SELEX) and phage display technology are two powerful technologies for identifying affinity reagent biomarkers. However, the benchtop protocols for both screening technologies are relatively lengthy and require well-trained personnel. We therefore developed a novel, integrated microfluidic system capable of automating SELEX and phage display technology. Instead of using cancer cell lines, it is the first work which used tissue slides as screening targets, which possess more complicated and uncovered information for affinity reagents to recognize. This allowed for the identification of aptamer (nucleic acid) and peptide probes specific to OvCa cells and tissues. Furthermore, this developed system could be readily modified to uncover affinity reagents for diagnostics or even target therapy of other cancer cell types in the future.

CASZ1 is a novel promoter of metastasis in ovarian cancer.

Epithelial ovarian cancer (EOC) carries the highest mortality rate of all gynecologic malignancies. This high mortality rate is attributed to the fact that most cases of ovarian cancer are detected at late stages when metastases are already present. Through microarray analysis, we previously demonstrated that castor zinc finger 1 (CASZ1) is up-regulated in EOC cells. In contrast to its role in EOC, CASZ1 functions a tumor suppressor in neuroblastoma. Human CASZ1 is predominantly expressed in 2 alternatively spliced isoforms: CASZ1a and CASZ1b. In the present study, we investigated the role of CASZ1 in ovarian cancer cell migration and invasion and assessed the value of CASZ1 expression as a prognostic indicator of metastasis in human ovarian cancer. We used a lentivirus expressing CASZ1-shRNA and a plasmid expressing CASZ1 from a CMV promoter to knockdown and overexpress CASZ1, respectively, in the MCAS, RMUG-S, TOV21G, and A2780(CP70) ovarian cancer cell lines. mRNA expression levels in tumor tissues and cell lines were measured using quantitative real-time PCR, and CASZ1 protein expression in EOC and paired metastatic tumor tissues was analyzed using immunohistochemistry. We found that CASZ1 was highly expressed in EOC tissues and ovarian cancer cell lines and that CASZ1 knockdown suppressed cell migration and invasion in EOC cells. CASZ1a and CASZ1b exerted similar effects on cell migration and invasion in EOC cells. In addition, CASZ1 promoted the epithelial-mesenchymal transition in EOC cells, and CASZ1 knockdown suppressed cancer metastasis in vivo. Furthermore, CASZ1 protein levels were elevated in human metastatic ovarian tumor tissues. Together, these results indicate that CASZ1 is a novel promoter of EOC metastasis and is highly up-regulated in metastatic EOC tumors.