To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower ...thoracic squamous cell esophageal carcinomas.
We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others.
We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%).
According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.
Mcl-1, an anti-apoptotic member of bcl-2 family, together with cleaved poly (ADC-ribose) polymerase (c-PARP) can serve as a marker of cell apoptosis. Previously we reported that treatment of Mnk ...inhibitor CGP57380 resulted in decreased Mcl-1 expression while increased c-PARP expression in non-small cell lung cancer (NSCLC) cells. In this study, we aimed to investigate association between Mcl-1 expression and clinicopathological features of NSCLC, and their correlation between Mcl-1 and both proliferation index (PI) and apoptotic index (AI) in NSCLC patients.
Tissue microarrays (TMA) including 350 cases of surgically resected NSCLC were utilize and stained with Mcl-1, Ki-67 and c-PARP antibodies, PI and AI were then evaluated, respectively.
Higher Mcl-1 expression and PI were observed in NSCLC compared with non-cancerous lung tissues (non-CLT), while AI was significantly lower in lung adenocarcinoma (ADC) compared with non-CLT. Additionally, Mcl-1 expression in lung ADC was evidently higher than that of in lung squamous cell carcinoma (SCC). The elevated Mcl-1 expression was associated with PI, and inversely related to AI in NSCLC. NSCLC patients with elevated Mcl-1 expression and high PI, or with high Mcl-1 expression and low AI had remarkably shorter overall survival time than these patients with low Mcl-1 expression.
Elevated expression of Mcl-1 might be inversely proportional to disease progression of NSCLC patients by promoting cell proliferation and inhibiting apoptosis, and Mcl-1 might serve as novel biomarker of poor prognosis for NSCLC patients.
Breast cancer has become the leading cause of cancer-related death among women. A large number of patients become resistant to drug chemotherapy. Paclitaxel (Taxol) is an effective chemotherapeutic ...agent used to treat cancer patients. Taxol has been widely used in human malignancies including breast cancer because it can stabilize microtubules resulting in cell death by causing an arrest during the G2/M phase of the cell cycle. Pro-apoptotic Bcl-2 antagonist killer 1 (Bak) plays an important role in Taxol-induced apoptosis in breast cancer. In our present study, we investigated the expression of the Bak protein and clinicopathological correlations in a large sample of breast cancer tissues by immunohistochemistry. We found that the percentage of high scores of Bak expression in breast cancer was significantly lower than that of the non-cancerous breast control tissue. In addition, lower Bak expression was positively associated with the clinical TNM stage of breast cancer with a significant decrease in overall survival compared with those with higher Bak expression especially in the Luminal and HER2 subtypes. Importantly, higher Bak expression predicted a favorable clinical outcome in the cases treated with Taxol indicated by a higher overall survival than that of patients with lower Bak expression especially in Luminal and HER2 subtypes. Furthermore, these results were confirmed in vitro since overexpression of Bak sensitized breast cancer cells to Taxol by inhibiting proliferation and promoting apoptosis; in contrast, downregulation of Bak through siRNA transfection inhibited Taxol induced-apoptosis. Therefore, our results demonstrate that Bak acts as a sensitive biomarker and favorable prognostic factor for Taxol treatment in breast cancer. The restoration of Bak expression would be therapeutically beneficial for Taxol resistant breast cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nonresolving inflammatory processes affect all stages of carcinogenesis. Lactoferrin, a member of the transferrin family, is involved in the innate immune response and anti-inflammatory, ...anti-microbial, and anti-tumor activities. We previously found that lactoferrin is significantly down-regulated in specimens of nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression, metastasis, and prognosis of patients with NPC. Additionally, lactoferrin expression levels are decreased in colorectal cancer as compared with normal tissue. Lactoferrin levels are also increased in the various phases of inflammation and dysplasia in an azoxymethane-dextran sulfate sodium (AOM-DSS) model of colitis-associated colon cancer (CAC). We thus hypothesized that the anti-inflammatory function of lactoferrin may contribute to its anti-tumor activity. Here we generated a new Lactoferrin knockout mouse model in which the mice are fertile, develop normally, and display no gross morphological abnormalities. We then challenged these mice with chemically induced intestinal inflammation to investigate the role of lactoferrin in inflammation and cancer development. Lactoferrin knockout mice demonstrated a great susceptibility to inflammation-induced colorectal dysplasia, and this characteristic may be related to inhibition of NF-κB and AKT/mTOR signaling as well as regulation of cell apoptosis and proliferation. Our results suggest that the protective roles of lactoferrin in colorectal mucosal immunity and inflammation-related malignant transformation, along with a deficiency in certain components of the innate immune system, may lead to serious consequences under conditions of inflammatory insult.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Nasopharyngeal carcinoma has a high incidence in southern China. The Wnt/ β -catenin signaling pathway plays a major role in cancer development and progression. Our current study aims to ...determine the clinical significance of the Wnt/ β -catenin pathway components such as β -catenin, cyclooxygenase 2, cyclin D1, c-Myc, and E-cadherin in 148 nasopharyngeal carcinomas by immunohistochemistry. We found that nasopharyngeal carcinoma stage T3 +T4 had significantly higher expression of β -catenin, cyclooxygenase 2, cyclin D1, and c-Myc and lower expression of E-cadherin than nasopharyngeal carcinoma stage T1 +T2 ( P < .001, P < .05, respectively).There was significantly higher expression of β -catenin ( P = .001) and cyclooxygenase 2 ( P = .003) and lower expression of E-cadherin ( P = .001) in nasopharyngeal carcinoma with lymph node metastasis than in nasopharyngeal carcinoma without lymph node metastasis. The expression of β -catenin in nasopharyngeal carcinoma was positively correlated with cyclooxygenase 2 ( r = 0.458, P < .0001), cyclin D1 ( r = 0.700, P < .0001), and c-Myc expression ( r = 0.144, P = .006) but negatively correlated with E-cadherin expression ( r = −0.601, P < .0001), respectively. The univariate analysis confirmed that overexpression of β -catenin and cyclooxygenase 2 and decreased expression of E-cadherin were significantly correlated with disease-free survival ( P < .01, P < .05, respectively). Overexpression of β -catenin and cyclooxygenase 2 and reduced expression of E-cadherin significantly correlated with a poor prognosis ( P = .005, P = .044, P = .019, respectively) by Kaplan-Meier survival curves and the log-rank test. Multivariate analysis indicated that high expression of β -catenin and decreased expression of E-cadherin were independent prognostic factors ( P = .002, P = .011, respectively) regardless of TNM stage and lymph node status. In conclusion, the aberrant high expression of β -catenin and decreased expression of E-cadherin is associated with poor prognosis in nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is the malignant tumor with ethnic and geographical distribution preference. Although intensity-modulated radiotherapy (IMRT)-based radiotherapy combined with ...chemotherapy and targeted therapy has dramatically improved the overall survival of NPC patients, there are still some patients suffering from recurrent tumors and the prognosis is poor. Multiple mechanisms may be responsible for radioresistance of NPC, such as cancer stem cells (CSCs) existence, gene mutation or aberrant expression of genes, epigenetic modification of genes, abnormal activation of certain signaling pathways, alteration of tumor microenvironment, stress granules (SGs) formation,
. We conduct a comprehensive review of the published literatures focusing on the causes of radioresistance, retrospect the regulation mechanisms following radiation, and discuss future directions of overcoming the resistance to radiation.
BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7
...–/–
) and BRD7
flox
/
flox
(BRD7
+/+
) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7
+/+
mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin–proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth
in vitro
and
in vivo
. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin–proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.
Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. Flotillin-2 (Flot-2) is not only an ...important component of cellular membrane, but also involves in various cellular processes such as membrane trafficking, T cell and B cell activation, regulation of several signaling pathways associated with cell growth and malignant transformation, keeping structure and junction of epidermal cells and formation of filopodia. Although such molecular effects of Flot-2 have been reported, whether the expression of Flot-2 protein is associated with clinicopathologic implication for NPC has not been reported. The purpose of this research is to investigate the expression of Flot-2 protein in NPC and control nasopharyngeal epithelial tissues by immunohistochemistry and elucidate the association between the expression of Flot-2 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of Flot-2 expression in the NPC, nasopharyngeal epithelia with atypical hyperplasia and in the control nasopharyngeal mucosa epithelia was 88.8% (119/134), 76.9% (10/13) and 5.7% (5/88), respectively. There was significantly higher expression of Flot-2 protein in NPC and nasopharyngeal epithelia with atypical hyperplasia compared to the control nasopharyngeal mucosa epithelia (P<0.001, respectively). The positive percentage of Flot-2 protein expression in NPC patients with lymph node metastasis was significantly higher than those without lymph node metastasis. Increasing of Flot-2 expression was obviously correlated with clinical stages of NPC patients. The expression of Flot-2 was proved to be the independent predicted factor for lymph node metastasis by multivariate analysis. The sensitivity of Flot-2 for predicting lymph node metastasis of NPC patients was 93%. Taken together, our results suggest that the increased expression of Flot-2 protein is a novel higher sensitivity biomarker that can predict lymph node metastases in NPC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Bone marrow stromal cells (BMSCs) have been implicated in multiple myeloma (MM) progression. However, the underlying mechanisms remain largely elusive. Therefore, we aimed to explore key ...factors in BMSCs that contribute to MM development.
Methods
RNA-sequencing was used to perform gene expression profiling in BMSCs. Enzyme-linked immunosorbent assays (ELISAs) were performed to determine the concentrations of PGE2 and TNFα in sera and conditioned media (CM). Western blotting, qRT-PCR and IHC were used to examine the expression of cyclooxygenase 2 (COX2) in BMSCs and to analyze the regulation of TNFα by COX2. Cell growth and adhesion assays were employed to explore the function of COX2 in vitro. A 5T33MMvt-KaLwRij mouse model was used to study the effects of COX2 inhibition in vivo.
Results
COX2 was found to be upregulated in MM patient-derived BMSCs and to play a critical role in BMSC-induced MM cell proliferation and adhesion. Administration of PGE2 to CM derived from BMSCs promoted MM cell proliferation and adhesion. Conversely, inhibition of COX2 in BMSCs greatly compromised BMSC-induced MM cell proliferation and adhesion. PCR array-based analysis of inflammatory cytokines indicated that COX2 upregulates the expression of TNFα. Subsequent rescue assays showed that an anti-TNFα monoclonal antibody could antagonize COX2-mediated MM cell proliferation and adhesion. Administration of NS398, a specific COX2 inhibitor, inhibited in vivo tumor growth and improved the survival of 5TMM mice.
Conclusions
Our results indicate that COX2 contributes to BMSC-induced MM proliferation and adhesion by increasing the secretion of PGE2 and TNFα. Targeting COX2 in BMSCs may serve as a potential therapeutic approach of treating MM.
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.
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