Abstract. Primary renal lymphoma (PRL) is a rare disease, with no more than 70 cases reported in the literature. The present study reports the case of a 70-year-old woman with PRL. The patient was asymptomatic, however, a mass on the right kidney was identified incidentally during routine physical examination. Computed tomography revealed a mass in the right kidney that was 3.6 cm in diameter. Subsequently, right nephrectomy was performed. The histological evaluation of the nephrectomy specimen showed diffuse large B-cell non-Hodgkin's lymphoma. The patient was treated with 6-8 cycles of a cyclophosphamide, epirubicin, vindesine and dexamethasone regimen. Follow-up examination performed after 2 months of treatment revealed no evidence of local recurrence. The present study also reviewed 49 cases of PRL that have been reported since 1989. It was found that a shorter survival time was experienced by patients with bilateral PRL (mean, 21 months) compared with unilateral PRL (mean, 68 months). A shorter survival time was also experienced by patients who were treated with chemotherapy only (mean, 15.8 months) compared with those who were treated with combination chemotherapy and surgery (mean, 49.4 months).
To investigate whether IL‐6 signaling affects the susceptibility of castration‐resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL‐6 levels) were developed by lentiviral transduction. While observing no secreted IL‐6 level in parental C4‐2 and CWR22Rv1 cells, we found the IL‐6 expression/secretion in these cells was induced after the transduction process and the IL‐6 level difference in C4‐2siIL‐6/sc and CWR22siIL‐6/sc cell CRPC cell sets could be detected. We then found that IL‐6‐knockdown cells were more susceptible to NK cell cytotoxicity than control cells due to lowered programmed death receptor ligand 1 (PD‐L1) and increased NK group 2D (NKG2D) ligand levels. In animal studies, to concur with the in vitro results, we found that IL‐6‐expressing cell‐derived tumors were more resistant to NK cell action than the tumors of IL‐6‐knockdown cells. Further, we discovered that JAK‐Stat3 is the most critical IL‐6 downstream signaling that modulates PD‐L1/NKG2D ligand levels in CRPC cells. Furthermore, inhibition of the JAK or Stat3 signaling effectively increased the susceptibility of C4‐2sc and CWRsc cells to NK cell cytotoxicity. We observed the most effective cytotoxicity when the PD‐L1 Ab and JAK inhibitor (or Stat 3 inhibitor) were used together. These results suggest that the strategy of targeting IL‐6 signaling (or its downstream signaling) may enhance the NK cell‐mediated immune action to CRPC tumors, thus yielding clinical implications in developing future immunotherapeutics of exploiting this strategy to treat patients with CRPC.
Abstract. Inflammation is regarded as one of the major hallmarks of tumors, and has a very close relationship with gastric cancer. Interleukin-33 (IL-33), a new member of the IL-1 family, plays an important role in both inflammatory disease and tumors. The present study was designed to explore the effects of IL-33 on the proliferation, drug sensitivity, and the invasiveness of gastric cancer cells in vitro. IL-33 at concentrations lower than 100 pg/ml did not alter the inhibitory rate of gastric cancer cells. Moreover, IL-33 at these low concentrations protected against platinum-induced apoptosis in various gastric cancer cell lines, yet not in normal gastric epithelial cells. We also found that IL-33 increased the activation of the JNK pathway, and enhanced the expression of ST2. Furthermore, SP600125, a selective inhibitor of the JNK pathway, significantly blocked the protective effects of IL-33 in gastric cancer cells. In addition, Matrigel invasion assay showed that IL-33 markedly promoted gastric cancer cell invasion. In conclusion, the present study demonstrated that IL-33 protected against platinum-induced apoptosis and promoted cell invasion via activation of the JNK pathway in gastric cancer cells. In light of the prevalence of platinumbased chemotherapeutics in the treatment of gastric cancer, our results suggest that the level of IL-33 should be monitored during the treatment of gastric cancer, particularly when using platinum-based chemotherapeutics. IntroductionGastric cancer is one of the most common types of cancers. Over 1.6 million individuals succumb to gastric cancer each year in China. The Chinese incidence of gastric cancer accounts for more than 40% of the worldwide occurrences. Moreover, the progression-free survival and overall survival rates of gastric cancer patients in China are much lower than those in Europe and the US. Therefore, research concerning the characteristics and pathogenesis of gastric cancer in Chinese patients is urgently needed.Gastric cancer can be influenced by a wide range of genetic and environmental factors. A clear association has been reported between gastric cancer and chronic inflammation (1-3). Pro-inflammatory factors, including interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF), may not only play roles in inflammation-associated carcinogenesis (4), but may also influence the chemotherapeutic sensitivity during gastric cancer treatment (5,6). IL-33 (previously known as NF-HEV), an 18-kDa protein, is a new member of the IL-1 family (7). Traditionally, the IL-1 family is well known for their effects on host defense, immune regulation and inflammation (7). However, recent research suggests that the IL-1 family is also involved in cancer development. For example IL-18, another member of the IL-1 family, acts as a pleiotropic cytokine in many types of cancer cells, and influences the invasion of gastric cancer cells under hypoxia (8). A high level of IL-18 in serum has been intensively associated with a wide variety of tumors, such as hepatocellular (9) a...
Inflammation is emerging as a new hallmark of cancer. Arachidonic acid (AA) metabolism, the family of cyclooxygenases (COXs) and lipoxygenase (LOX) play important roles in AA-related inflammatory cascades. In 94 colorectal cancer samples collected from the Han population, the immunohistochemical results indicated that 68% of the patients with colorectal cancer had a co-expression of both COX-2 and 5-LOX, while both displayed low expression in the matched normal tissues. In cell lines, three colorectal cancer cell lines exhibited high expression of COX-2 and 5-LOX. During stable silencing of the expression of COX-2 or 5-LOX in LoVo cancer cells, we found that downregulation of either COX-2 or 5-LOX significantly diminished the growth, migration and invasion of the colon cancer cells and specifically, downregulation of COX-2 could elicit upregulation of 5-LOX protein and vice versa. The above results suggested that the simultaneous blocking of COX-2 and 5-LOX activity may bring more potential benefits in managing the progression of colon cancer. Therefore, we sought to explore the effectiveness of a dual COX-2/5-LOX inhibitor darbufelone on the proliferation, migration, invasion and apoptosis of colon cancer cells, as well as the underlying mechanism of action. The results indicated that darbufelone significantly decreased the proliferative and invasive abilities of the colon cancer cells, in a dose-dependent manner. During the study of the related mechanisms, we found an upregulation of p27 and downregulation of cyclin D1 as well as CDK4 after darbufelone treatment, which indicated that darbufelone could arrest the cell cycle of LoVo cells at the G0/G1 phase. Furthermore, the activation of caspase-3 and -9, upregulation of Bax and downregulation of Bcl-2 demonstrated the occurrence of apoptosis by darbufelone. Finally, darbufelone also prevented the migration and invasion of LoVo cells, which may be ascribed to the upregulation of E-cadherin and ZO-1. In summary, our data suggest that the inhibition of both COX-2/5-LOX may be an effective therapeutic approach for colon cancer management, particularly for those patients with high expression of COX-2/5-LOX.
Background LncRNAs have recently emerged as vital regulators in the pathogenesis and development of various cancers. LncRNA PVT1 is reported to function as an oncogene in some tumors. However, the role of PVT1 in RCC remains unknown. Purpose To explore the potential effects of lncPVT1 on the development of renal cell carcinoma. Methods The expression of PVT1 in renal cancer cell lines and tissues was measured by qRT-PCR. The endogenous PVT1 was silenced by RNAi. Cell viabilities were measured by the MTT assay. The migration and invasion of cells were investigated by the transwell assay. The apoptosis of cells was measured by the Nucleosome ELISA and caspase-3 activity assays. The levels of proteins were measured by the western blot. Results We found that PVT1 was upregulated in RCC tissues compared with the adjacent normal tissues. PVT1 expression was closely correlated with TNM stage, Fuhrman grade, lymph node metastasis and tumor size. Kaplan–Meier analysis revealed that high expression of PVT1 was significantly associated with poor overall survival. In accordance, overexpression of PVT1 was observed in RCC cells comto HK-2 cell. Silencing of PVT1 significantly repressed cell viability, induced apoptosis and inhibited cell migration and invasion in vitro. Furthermore, bioinformatic analysis and luciferase reporter assay confirmed that miR-16-5p was a target of PVT1. Silencing of miR-16-5p mostly reversed the regulatory effects on RCC cells induced by downregulation of PVT1. Conclusion In summary, our study indicates that targeting PVT1 might represent a rational therapeutic strategy for RCC.
Phosphodiesterase type 5 (PDE5) plays a key role in regulating the intracellular cyclic GMP (cGMP) concentration, which influences anti-proliferative and pro-apoptotic mechanisms in multiple carcinomas. PDE5 inhibitors, such as exisulind and its analogs have anticancer activities. In this study, we found that suppressing PDE5 gene expression by PDE5 siRNA inhibited cell proliferation and induced apoptosis in OS-RC-2 human renal cell carcinoma cells. These effects were enhanced by 8-Br-cGMP, a cell membrane permeable cGMP derivative, and were inhibited by KT5823, a protein kinase G (PKG) inhibitor, indicating that PKG was activated by intracellular cyclic GMP. In addition, there was a reduction in both the mRNA and protein expression of cyclin D1, while p21 protein expression was increased; the reduction in cyclin D1 expression was blocked by the proteasome inhibitor, MG132, or c-Jun N-terminal kinase (JNK) inhibitor; both β-catenin and JNK were phosphorylated by activated PKG. Furthermore, p21 protein expression was decreased in Sp1 siRNA transfected-cells treated with 8-Br-cGMP, indicating that p21 may be partly controlled by the PKG activation through Sp1. Furthermore, we found that PKG Iβ was responsible for the anticancer activities. Our findings indicate that the downregulation of PKG-activated genes, such as cyclin D1 partly accounts for the pro-apoptotic effects in PDE5 siRNA-transfected OS-RC-2 cells.
Early diagnosis and surveillance for metastasis and recurrences are critical issues of urologic cancer. Deregulation of long non-coding RNAs (lncRNAs) has been implicated in urologic malignancies and represents potential markers or therapeutic targets. However, the utility of lncRNA as biomarkers appears to be overstated due to heterogeneous or irreproducible results from different studies. Thus, a critical and cautious review on the biomarker potential of lncRNAs is needed. This review provides an update on new findings of lncRNA-based markers for urologic cancer. The diverse mechanisms and associated examples of lncRNAs involved during the carcinogenesis of prostate cancer, bladder cancer and renal cancer were discussed in a more balanced and critical manner, as were the suitability of lncRNAs as diagnostic or prognostics markers.
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