The records of 24 patients with renal cell carcinoma involving the inferior vena cava who were free of metastatic disease at presentation were reviewed retrospectively. The over-all 2-year survival for the group was 45.8 per cent, with a mean survival of 38.9 months. When the group was analyzed according to the level of extension of the vena caval thrombus marked differences in the rate of survival and of incidence of local progression of disease were found. The 10 patients with an infrahepatic vena caval thrombus had a 2-year survival rate of 80 per cent and a mean survival of 61.4 months. Two patients (20 per cent) had extension of tumor into the perinephric fat and none had involvement of the regional lymph nodes. The 14 patients with a vena caval thrombus extending to the level of the hepatic veins or beyond had a 2-year survival rate of 21 per cent and a mean survival of 22.9 months. Tumor was present in the regional lymph nodes and/or perinephric fat in 9 of these patients (64 per cent). These results suggest that the level of vena caval involvement by tumor thrombus in patients with renal cell carcinoma has prognostic significance.
The nature and extent of mucosal alterations in 30 consecutive surgical specimens removed for urothelial neoplasia were evaluated by systematic mapping. The findings correlated with pertinent pathological, cytological and clinical data. Generally, the grade of the principal neoplasm paralleled the degree of epithelial disturbance in the grossly normal urothelium, high grade carcinomas being associated consistently with severe changes and low grade cancers with hyperplasia only. Cytological studies reflected accurately the grade of the principal neoplasm, and the presence of concomitant contiguous and remote mucosal abnormalities.
Purpose
The development of new effective therapeutic agents with minimal side effects for prostate cancer treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine – Qing Dai (Indigo Naturalis), has been used to treat leukemia for decades. However, the anti-cancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in prostate cancer.
Experimental Design
Human prostate cancer cell lines were treated with or without Natura-alpha followed by cell growth and invasion assays measured. The anti-tumor effects of Natura-alpha were examined in nude mice tumor xenograft models, as well as in a patient with advanced hormone refractory metastatic prostate cancer. Signal network proteins targeted by Natura-alpha were analyzed using Proteomic Pathway Array Analysis (PPAA) on xenografts.
Results
Natura-alpha inhibited the growth of both androgen-dependent (LNCaP), and androgen-independent (LNCaP-AI, PC-3, and DU145) prostate cancer cells with IC50 between 4 to 10 Μm, also inhibits invasion of androgen-independent prostate cancer cells. Its anti-tumor effects were further evident in vivo tumor reduction in androgen-dependent and -independent nude mice tumor xenograft models as well as reduced tumor volume in the patient with hormone refractory metastatic prostate cancer. PPAA revealed that anti-proliferative and anti-invasive activities of Natura-alpha on prostate cancer might primarily be through its down-regulation of Forkhead box M1 (FOXM1) protein. Forced over-expression of FOXM1 largely reversed the inhibition by Natura-alpha.
Conclusion
Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone sensitive and hormone refractory prostate cancer with minimal side effects.
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