ABSTRACT
@#Renal cell carcinoma is the most common renal malignancy in adults and extremely rare in children.It may present with hematuria, flank pain and palpable mass. Treatment protocols for renal cellcarcinoma in children have not yet been well-defined due to the rarity of the desease, however surgeryremains the mainstay treatment for tumors that are resectable. Presented here is a case of a 1 year oldfemale presenting with left hemiabdominal mass, who underwent transabdominal left radicalnephrectomy. Histopathology showed a papillary renal cell carcinoma type 1, with positiveimmunohistochemical stains for Vimentin, CK7 and AMACR.
Subject(s)
VimentinABSTRACT
To investigate the effect of licochalcone (LCA) on autophagy in renal cell carcinoma (RCC), and further determine whether the mechanism is correlated with the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway, RCC 786-O and 769-P were used as study subjects. MTT assay was used to examine cell proliferation. The abilities of migration and invasion were detected by Transwell. The autophagy was observed under the fluorescence microscope through acridine orange staining. Green fluorescence spots were observed in Ad-GFP-LC3 transfection experiment. The protein expression was detected by Western blot. MTT assay results showed a dose and time-dependent cytotoxicity in the two cell lines treated with LCA. LCA inhibited migration and invasion in 786-O and 769-P cells. LCA increased the expression levels of LC3-Ⅱ, beclin 1, Atg5, and down-regulated the expression of p62. In addition, LCA inhibited the PI3K/Akt/mTOR pathway. Furthermore, the inhibition of PI3K/Akt by LY294002 or that of mTOR by rapamycin augmented LCA-induced autophagy. The findings demonstrated that LCA inhibited the proliferation, migration, invasion, and induced autophagy by inactivating PI3K/Akt/mTOR signaling pathway in 786-O and 769-P cells.
ABSTRACT
MicroRNAs (miRNAs) modulate the expression of tumorigenesis-related genes and play important roles in the development of various types of cancers. It has been reported that miR-144 is dysregulated and involved in multiple malignant tumors, but its role in renal cell carcinoma (RCC) remains elusive. In this study, we demonstrated miR-144 was significantly downregulated in human RCC. The decreased miR-144 correlated with tumor size and TNM stage. Moreover, overexpression of miR-144 in vitro suppressed RCC cell proliferation and G2 transition, which were reversed by inhibition of miR-144. Bioinformatic analysis predicted that mTOR was a potential target of miR-144, which was further confirmed by dual luciferase reporter assay. Additionally, the examination of clinical RCC specimens revealed that miR-144 was inversely related to mTOR. Furthermore, knocking down mTOR with siRNA had the same biological effects as those of miR-144 overexpression in RCC cells, including cell proliferation inhibition and S/G2 cell cycle arrest. In conclusion, our results indicate that miR-144 affects RCC progression by inhibiting mTOR expression, and targeting miR-144 may act as a novel strategy for RCC treatment.
Subject(s)
Female , Humans , Male , Middle Aged , Carcinoma, Renal Cell , Genetics , Metabolism , Pathology , Case-Control Studies , Cell Line, Tumor , Cell Proliferation , G2 Phase , Kidney Neoplasms , Genetics , Metabolism , Pathology , MicroRNAs , Genetics , Metabolism , S Phase , TOR Serine-Threonine Kinases , Genetics , MetabolismABSTRACT
Purpose: Brain metastases from renal cell carcinoma (RCC) have been successfully treated with stereotactic radiosurgery (SRS). Metastases to extra-cranial sites may be treated with similar success using stereotactic body radiation therapy (SBRT), where image-guidance allows for the delivery of precise high-dose radiation in a few fractions. This paper reports the authors’ initial experience with image-guided SBRT in treating primary and metastatic RCC. Materials and methods: The image-guided Brainlab Novalis stereotactic system was used. Fourteen patients with 23 extra-cranial metastatic RCC lesions (orbits, head and neck, lung, mediastinum, sternum, clavicle, scapula, humerus, rib, spine and abdominal wall) and two patients with biopsy-proven primary RCC (not surgical candidates) were treated with SBRT (24-40 Gy in 3-6 fractions over 1-2 weeks). All patients were immobilised in body cast or head and neck mask. Image-guidance was used for all fractions. PET/CT images were fused with simulation CT images to assist in target delineation and dose determination. SMART (simultaneous modulated accelerated radiation therapy) boost approach was adopted. 4D-CT was utilised to assess tumour/organ motion and assist in determining planning target volume margins. Results: Median follow-up was nine months. Thirteen patients (93%) who received SBRT to extra-cranial metastases achieved symptomatic relief. Two patients had local progression, yielding a local control rate of 87%. In the two patients with primary RCC, tumour size remained unchanged but their pain improved, and their renal function was unchanged post SBRT. There were no significant treatment-related side effects. Conclusion: Image-guided SBRT provides excellent symptom palliation and local control without any significant toxicity. SBRT may represent a novel, non-invasive, nephron-sparing option for the treatment of primary RCC as well as extra-cranial metastatic RCC.
ABSTRACT
Surgery is the only curative treatment modality for renal cell carcinoma (RCC). However, approximately 30% of patients who undergo successful nephrectomy for RCC will develop locoregional or metastatic recurrence. Effective treatment for recurrent or metastatic RCC is limited. It is known that conventional radiation therapy and chemotherapy are relatively ineffective for RCC patients with distant metastases. Although immune therapy with high dose interleukin can provide disease control for a portion of patients with advanced RCC, its therapeutic effect usually is not sustainable. In addition, substantial adverse effects and complications have limited the use of high dose interleukin treatment. Advances in the understanding at the molecular level of cancer have led to much progress in the development of anti-cancer agents, including drugs of targeted cancer therapy. Targeted therapy is not only effective in cancer treatment, but also has reduced adverse effects compared with conventional chemotherapy and immune therapy. Much progress in the treatment of advanced RCC by targeted therapy has been achieved in recent years. In this review, we will illustrate the roles, mechanisms and effects of several targeted therapy agents, including the two newly FDA-approved drugs, sorafenib and sunitinib, in the treatment of advanced renal cell carcinoma.