Bone and soft tissue sarcomas with complex and varied clinical, imaging, and pathological characteristics cannot be diagnosed and treated by a single discipline, as each discipline has some ...limitations. This study aimed to explore the role of a multidisciplinary team (MDT) in the diagnosis and treatment of bone and soft tissue sarcomas over the past four consecutive years. The subjects were 269 patients discussed during MDT meetings at a Bone and Soft Tissue Sarcomas Center in South China. The diagnosis, relapse diagnosis, unplanned resection, management of pulmonary nodules, and treatment of refractory and advanced tumors were compared to similar data provided in the literature to (i) determine whether the MDT significantly affected the diagnosis and treatment of bone and soft tissue sarcomas, and (ii) explore trends in the types of patients with bone and soft tissue sarcomas and treatment decision-making since the establishment of the MDT. Results revealed that the MDT significantly improved preoperative diagnostic accuracy for patients with bone and soft tissue sarcomas; the accuracy of diagnosis and relapse diagnosis by the MDT reached 95.42% and 100%, respectively. After an MDT discussion, the positive pathology rate for extended resection after unplanned resection was 81.2%. The overall accuracy of the MDT in determining the nature of pulmonary nodules was 87.1-91.9%. For patients presenting with pulmonary nodules in osteosarcoma, no statistically significant difference in survival was shown between cases discussed by the MDT and those without an MDT discussion (
= 0.5751). Collectively, the MDT can play a positive role in accurate preoperative diagnosis, relapse diagnosis, the decision to extend resection after an unplanned resection, and the diagnostic accuracy of pulmonary nodules.
Eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting factor for cap-dependent translation initiation, which is known to regulate oncogenesis. Elevated eIF4E and its negative ...impact on prognosis in human non-small cell lung cancer (NSCLC) have been reported previously. However, its potential as a therapeutic target and role in regulation of sensitivity to EGFR inhibitors is an area of ongoing investigations. In this study, we detected increased levels of eIF4E in 16 human NSCLC cell lines compared with their normal bronchial epithelial cells. Consistently, human tissue array analysis showed that eIF4E expression was significantly higher in human NSCLC tissues than normal tissues. Inhibition of eIF4E using eIF4E siRNA inhibited the growth and invasion of NSCLC cells. These data suggest that eIF4E overexpression plays a crucial role in positive regulation of the growth and invasion of NSCLC cells. By proteomics, we found that eIF4E levels were elevated in erlotinib-resistant cell lines compared with the sensitive parental cell line. In agreement, assembly of the eIF4F cap complex and several oncogenic proteins regulated by the cap-dependent translation mechanism, were also increased in erlotinib-resistant cells. Thus, erlotinib-resistant cells exhibit elevated eIF4E expression and cap-dependent translation. Inhibition of eIF4F with different means (e.g., gene knockdown) downregulated c-Met expression and partially restored cell sensitivity to erlotinib, suggesting that elevated eIF4E contributes to development of erlotinib resistance, likely through positive regulation of c-Met expression. Taken together, we suggest that elevated eIF4E in NSCLC cells is associated with proliferation, invasion and acquired erlotinib resistance.
Great efforts have been made to develop novel and efficacious therapeutics against pancreatic cancer to improve the treatment outcomes. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) ...is such a therapeutic cytokine with selective killing effect toward malignant cells. However, some human pancreatic cancers are intrinsically resistant to TRAIL-mediated apoptosis or therapy. In this study, we have shown that the histone deacetylase inhibitor LBH589 can synergize with TRAIL to augment apoptosis even in TRAIL-resistant cells. LBH589 decreased c-FLIP levels in every tested cell line and survivin levels in some of the tested cell lines. Enforced expression of ectopic c-FLIP, but not survivin, abolished the cooperative induction of apoptosis by the combination of LBH589 and TRAIL, indicating that c-FLIP downregulation plays a critical role in LBH589 sensitization of pancreatic cancer cells to TRAIL. Moreover, LBH589 decreased c-FLIP stability and the presence of the proteasome inhibitor MG132 prevented c-FLIP from reduction by LBH589. Correspondingly, we detected increased levels of ubiqutinated c-FLIP in LBH589-treated cells. These data thus indicate that LBH589 promotes ubiqutin/proteasome-mediated degradation of c-FLIP, leading to downregulation of c-FLIP. Collectively, LBH589 induces c-FLIP degradation and accordingly sensitizes pancreatic cancer cells to TRAIL-induced apoptosis, highlighting a novel therapeutic regimen against pancreatic cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lung cancer is a leading cause of cancer deaths worldwide, consisting of two major histological subtypes: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). In some cases, NSCLC ...patients may undergo a histological transformation to SCLC during clinical treatments, which is associated with resistance to targeted therapy, immunotherapy, or chemotherapy. The review provides a comprehensive analysis of SCLC transformation from NSCLC, including biological mechanism, clinical relevance, and potential treatment options after transformation, which may give a better understanding of SCLC transformation and provide support for further research to define better therapy options.
Objective To observe the expressions of phosphorylated eukaryotic translation initiation factor 4E (p-eIF4E) and phospho-eIF4E-binding protein 1 (p-4EBP1) and investigate their associations with ...clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). Methods We detected the expressions of p-eIF4E and p-4EBP1 proteins by immunohistochemistry in NPC tissues (n=314 cases), and analyzed the associations between the expressions of p-eIF4E and p-4EBP1 proteins and clinicopathological features and prognosis in NPC by SPSS16.0. Results Positive rates of p-eIF4E and p-4EBP-1 proteins in NPC were 74.2% (233/314) and 72.9% (229/314), respectively. There were significantly higher expressions of p-eIF4E and p-4EBP-1 proteins in the cases with lymph node metastasis than in those without lymph node metastasis. However, no significant correlations were observed between the expressions of p-eIF4E and p-4EBP-1 proteins and the age, gender, histological type, and clinical stage. There was significantly pos
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The molecular chaperone protein HSP60 is mainly distributed in mitochondria and assists protein folding under physiological and pathological conditions. Accumulating evidence suggests ...abnormally expressed HSP60 in cancer is associated with clinicopathological features and prognosis of cancer patients. HSP60 could be used as a new biomarker for both diagnostic and prognostic purpose and tumor therapy. In this review article, we briefly described the structure, functional cycle, and regulatory mechanism of HSP60, and summarized its functional diversity in cancer as well as recent progress related to the diagnostic application of HSP60 and inhibitors against HSP60, which could provide us a comprehensive understanding about the value of HSP60 in tumor management.
Summary Fatty acid synthase–associated protein with death domain (FADD) is a key adaptor protein that bridges a death receptor (eg, death receptor 5) to caspase 8 to form the death-inducing signaling ...complex during apoptosis. The expression and prognostic impact of FADD in nasopharyngeal carcinoma (NPC) have not been well studied. This study focused on detecting FADD expression and analyzing its prognostic impact on NPC. FADD expression was assessed on pretreatment tumor tissues of 248 cases of NPC patients and 76 cases of noncancerous nasopharyngeal control tissue. The results showed that the positive percentage of FADD expression in NPC (63.7%, 158/248) was significantly higher than that in the noncancerous nasopharyngeal control tissues (28.9%, 22/76) ( P < .0001). The positive expression of FADD in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis ( P = .009). Furthermore, FADD expression was more pronouncedly increased in metastatic NPC than the matched primary NPC tissues ( P = .017). Both univariate and multivariate survival analysis indicated that increased FADD expression was significantly correlated inversely with overall survival in NPC patients ( P = .003 and P = .007, respectively). Taken together, high expression of FADD may be an independent biomarker for poor prognosis in NPC.
Death receptor 5 (DR5) and caspase-8 are major components in the extrinsic apoptotic pathway. The alterations of the expression of these proteins during the metastasis of head and neck squamous cell ...carcinoma (HNSCC) and their prognostic impact have not been reported. The present study analyzes the expression of DR5 and caspase-8 by immunohistochemistry (IHC) in primary and metastatic HNSCCs and their impact on patient survival. Tumor samples in this study included 100 primary HNSCC with no evidence of metastasis, 100 primary HNSCC with lymph node metastasis (LNM) and 100 matching LNM. IHC analysis revealed a significant loss or downregulation of DR5 expression in primary tumors with metastasis and their matching LNM compared to primary tumors with no evidence of metastasis. A similar trend was observed in caspase-8 expression although it was not statistically significant. Downregulation of caspase-8 and DR5 expression was significantly correlated with poorly differentiated tumors compared to moderately and well differentiated tumors. Univariate analysis indicates that, in HNSCC with no metastasis, higher expression of caspase-8 significantly correlated with better disease-free survival and overall survival. However, in HNSCC with LNM, higher caspase-8 expression significantly correlated with poorer disease-free survival and overall survival. Similar results were also generated when we combined both DR5 and caspase-8. Taken together, we suggest that both DR5 and caspase-8 are involved in regulation of HNSCC metastasis. Our findings warrant further investigation on the dual role of caspase-8 in cancer development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ezrin, the linker between membrane protein and cytoskeleton, plays an important role in the cellular morphology, cytoskeleton reorganization, adhesion, invasion and metastasis. In this study, ezrin ...was found to express in high levels either in nasopharyngeal carcinoma tissues or in nasopharyngeal carcinoma 5‐8F cells and the knockdown of ezrin expression in the 5‐8F cells by RNA interferance could reduce invasive ability, suggesting that ezrin is involved in the progression and invasion of nasopharyngeal carcinoma. Nasopharyngeal carcinoma‐associated gene 6 is a novel candidate suppressor gene of tumor metastasis, which was originally cloned in nasopharyngeal carcinoma high‐frequency heterozygosity loss region 9p21‐22 and is down‐regulated in nasopharyngeal carcinoma. In the present study, we hypothesize that nasopharyngeal carcinoma‐associated gene 6 plays an inhibitory role in the migration and invasion of nasopharyngeal carcinoma cells via modulating the function of ezrin. Firstly, different mutants of NGX6 were constructed and transfected into nasopharyngeal carcinoma 5‐8F cells. The invasion and migration of 5‐8F cells overexpressing nasopharyngeal carcinoma‐associated gene 6 or mutants were measured. The results showed that enhanced expression of nasopharyngeal carcinoma‐associated gene 6 could reduce invasive and migratory abilities of 5‐8F cells, and the cytoplasmic domain was essential for nasopharyngeal carcinoma‐associated gene 6 to modulate cell migration and invasion. Further experiment results showed that nasopharyngeal carcinoma‐associated gene 6 protein was associated with ezrin by its cytoplasm region, and it could down‐regulate the expression level of ezrin. These results demonstrated that nasopharyngeal carcinoma‐associated gene 6 was probably involved in the modulation of invasive and adhesive ability of nasopharyngeal carcinoma cells by down‐regulating the expression level of ezrin. (Cancer Sci 2007; 98: 341–349)
Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this ...functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growth in vitro and tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.
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