Background: P21^(WAF1/Cip1) binds to cyclin-dependent kinase complexes and inhibits their activities. It was originally described as an inhibitor of cancer cell proliferation. However, many recent studies have shown that p21 promotes tumor progression when accumulated in the cell cytoplasm. So far, little is known about the correlation between cytoplasmic p21 and drug resistance. This study was aimed to investigate the role of p21 in the cisplatin resistance of ovarian cancer. Methods: RT-PCR, western blot and immunofluorescence were used to detect p21 expression and location in cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008. Regulation of cytoplasmic p21 was performed through transfection of p21 siRNA, Akt2 shRNA and Akt2 constitutively active vector in the two cell lines; their effects on cisplatin-induced apoptosis were evaluated by flow cytometry. Tumor tissue sections of clinical samples were analyzed by immunohistochemistry. Results: p21 predominantly localizes to the cytoplasm in C13* compared to OV2008. Persistent exposure to low dose cisplatin in OV2008 leads to p21 translocation from nuclear to cytoplasm, while it had not impact on p21 localization in C13*. Knockdown of cytoplasmic p21 by p21 siRNA transfection in C13* notably increased cisplatin-induced apoptosis through activation of caspase 3. Inhibition of p21 translocation into the cytoplasm by transfection of Akt2 shRNA into C13* cells significantly increased cisplatin-induced apoptosis, while induction of p21 translocation into the cytoplasm by transfection of constitutively active Akt2 in OV2008 enhanced the resistance to cisplatin. Immunohistochemical analysis of clinical ovarian tumor tissues demonstrated that cytoplasmic p21 was negatively correlated with the response to cisplatin based treatment. Conclusions: Cytoplasmic p21 is a novel biomarker of cisplatin resistance and it may represent a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.

Background: Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells. Methods: We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID₅₀ assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods. Results: Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice. Conclusions: These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects.

Cesarean scar pregnancy (CSP) may lead to varying degrees of complications. There are many treatment methods for it, but there is no unified or recognized treatment strategies. The study of systematic review and network meta-analysis is to observe the efficacy and safety of treatment modalities for patients with CSP. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from their inception to January 31, 2024. Additionally, relevant reviews and meta-analyses were manually searched for additional references. Our study incorporated head-to-head trials involving a minimum of ten women diagnosed with CSP through ultrasound imaging or magnetic resonance imaging (MRI), encompassing a detailed depiction of primary interventions and any supplementary measures. Trials with a Newcastle-Ottawa Scale (NOS) score below 4 were excluded due to their low quality. We conducted a random-effects network meta-analysis and review for cesarean scar pregnancy. Group-level data on treatment efficacy and safety, reproductive outcomes, study design and demographic characteristics were extracted following a predefined protocol. Studies' quality was assessed using the Cochrane risk-of-bias tools for randomized controlled trials (RCT) and the Newcastle‒Ottawa scale (NOS) for cohort studies and case series. The main outcomes were efficacy (initial treatment success) and safety (complications), of which summary odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) using pairwise and network meta-analysis with random effects. Seventy-three trials (7 RCTs) assessing a total of 738369 women and 17 treatment modalities were included. Network meta-analyses were rooted in data from 7373 trials that reported success rates and 55 trials that reported complications. The findings indicate that laparoscopy (Lap), transvaginal resection (TVR), hysteroscopic curettage (Hys) and High-intensity focused ultrasound combined with suction curettage (HIFU+SC) demonstrated the highest cure rates, as evidenced by SUCRA rankings of 91.2, 88.2, 86.9 and 75.3, respectively. When compared to suction curettage (SC), the odds ratios of efficacy were 6.76 (1.99, 23.01) for Lap, 5.92 (1.47, 23.78) for TVR, 5.00 (1.99, 23.78) for Hys and 3.27 (1.08, 9.89) for HIFU+SC. Complications were more likely to occur after receiving uterine artery chemoembolization (UACE), SC, MTX+Hys and sMTX; Hys, HIFU+SC and Lap were safer than the other options derived from finite evidence; and the confidence intervals of all the data were wide. Our findings indicate that Lap, TVR, Hys and HIFU+SC procedures exhibit superior efficacy with reduced complications. The utilization of methotrexate (both locally guided injection and systemic administration) as a standalone medical treatment is not recommended.

Study objective: Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy associated with severe complications, including significant hemorrhage, the potential need for hysterectomy, and life-threatening risks. Currently, two classification methods exist for CSP: Vial (type I^a and II^a) and Chinese Expert’s Consensus (type I^b, type II^b, and type III^b). However, these methods have limitations in guiding the selection of appropriate treatment plans for CSP. The purpose of this study was to systematically evaluate the effectiveness of various treatments for CSP within our clinic. Method: Our study included 906 patients with CSP from January 2013 to December 2018. The chi-squared test and logistic analysis were used to compare the clinical characteristics. The median and interquartile range (IQR) was calculated. We also analyzed whether preoperative application of methotrexate (MTX) could improve surgical outcomes and the relevant characteristics of misdiagnosed CSP patients. Results: There was a significant difference in gestational age, gestational sac diameter, gestational sac width, gestational sac area, remnant myometrial thickness, vaginal bleeding and preoperative hemoglobin levels (p < 0.001) but not in the incidence of residual tissue (p = 0.053). The other factors (intraoperative blood loss, hemoglobin decline, first hemoglobin after operation, total hospital stay, hospital stay after operation, transfusion and duration of catheter drain) were significantly different (p < 0.001). For type I^a and type I^b CSP, 39.3% and 40.2% of patients were treated with dilatation and curettage (D&E) under ultrasound, respectively. For type II^a and type III^b CSP, 29.9% and 62.7% of patients were treated with laparotomy, respectively. There were no differences in surgical methods, residual tissue and reoperation between the MTX and non-MTX groups (p = 0.20), but liver damage, hospital stay and pain perception were more remarkable in the MTX group. It is noteworthy that 14% of the patients were misdiagnosed with an intrauterine pregnancy. The incidence of misdiagnosis in type II^a CSP patients was higher than that in type I^a CSP patients (p < 0.001). Conclusion: For type I CSP patients, D&E under ultrasound or D&E under hysteroscopy should be recommended. For type III^b CSP patients, operative resection should be used. It is currently difficult to choose the appropriate treatment methods for type II^a or type II^b CSP patients.

Objective: Cesarean scar pregnancy (CSP) can have catastrophic consequences, but a standardized diagnosis and treatment for CSP are lacking. At least 10 different treatments are currently available, further confusing treatment selection. The aim of this study was to compare the outcomes of using laparotomy or laparoscopy to treat CSP. Methods: We reviewed data from 935 patients with suspected CSP from 1 January 2013 to 31 December 2018. A total of 278 patients were included in the study, of whom 121 were treated with laparoscopy and 157 were treated with laparotomy. We compared and analyzed the characteristics of laparoscopic and open surgeries for treating CSP cases and the advantages and disadvantages of different vascular pretreatments. Results: Intraoperative bleeding, the transfusion rate, total days of hospitalization and postoperative hospital length of stay were lower with laparoscopy than laparotomy (P < 0.05). There was no difference in the factors (beta human chorionic gonadotropin [β-HCG] decrease, reoperation rate and tissue residues) closely related to the success of the surgery in the two groups. Furthermore, we used different blood vessel pretreatments among patients. The rates of tissue residue, reoperation and intraoperative blood transfusion were lower in patients with temporary vascular occlusion than in patients with permanent vascular occlusion. Conclusion: This study revealed that laparoscopic surgery is superior to laparotomic surgery for treating CSP. Patients in both groups benefited from temporary arterial occlusion. Thus, temporary arterial occlusion with laparoscopic surgery may be the best treatment for CSP.