PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.
In childhood, two distinct patterns of LAHS are observed, either associated with infection or autoimmune disease. Initial diagnostic investigations are critical to differentiating these two patterns as the prognosis and outcome for each is distinct.
The synthesized gold nanoparticles using indole-3-carbinol (AuNPI3Cs) has been characterized and its antineoplastic activities has been studied here. Several techniques have been used to characterize the AuNPI3Cs. Ultraviolet spectroscopy studies indicated the stability of the synthesized AuNPI3Cs, while FTIR analysis proved that indole-3-carbinol was playing an important role in stabilizing the AuNPI3Cs.TEM analysis study showed that AuNPI3Cs were mostly spherical in shape with an average particle size of 3 nm. The selected area electron diffraction pattern exhibited the crystalline nature of AuNPI3Cs, which was further proved by XRD studies. The present study describes the in vitro antineoplastic efficacy of AuNPI3Cs against Ehrlich ascites carcinoma (EAC) cells. Results showed that the IC 50 dose of AuNPI3Cs was significantly capable of elevating intracellular reactive oxygen species. AuNPI3Cs induced apoptosis by increasing the G 2 /M population, LIVE/DEAD cytotoxicity, chromatin condensation, DNA laddering and TUNEL-positive cells significantly (p < 0.001). Reduction of the mitochondrial potential by AuNPI3Cs was substantiated by JC-1 fluorescent staining. These findings will enlighten future biomedical applications of gold nanoparticles using indole-3-carbinol (AuNPI3Cs) as an antineoplastic agent.
Drug preparation from AuNPI3CAuNPI3Cs (1 mg ml À1 stock) were prepared by concentrating the solution with RPMI media. The solution of AuNPI3Cs was then sonicated and was used for the assessment of biopharmacological activities.56436 | RSC Adv., 2016, 6, 56435-56449This journal is
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