Construction of a prognostic model for extensive-stage small cell lung cancer patients undergoing immune therapy in northernmost China and prediction of treatment efficacy based on response status at different time points.

BACKGROUND AND PURPOSE: Recently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients. METHODS: This research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients' overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell's C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan-Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26. RESULTS: This study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell's C-index in the training and validation sets of the model was 0.85 (95% CI 0.76-0.93) and 0.88 (95% CI 0.76-0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy. CONCLUSION: This study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy.

Exploration of factors affecting hemodynamic stability following pheochromocytoma resection - cohort study.

Purpose: Surgery is the only way to cure pheochromocytoma; however, postoperative hemodynamic instability is one of the main causes of serious complications and even death. This study's findings provide some guidance for improved clinical management. Patients and methods: This study was to investigate the factors leading to postoperative hemodynamic instability in the postoperative pathology indicated pheochromocytoma from May 2016 to May 2022. They were divided into two groups according to whether vasoactive drugs were used for a median number of days or more postoperatively. The factors affecting the postoperative hemodynamics in the perioperative period (preoperative, intraoperative, and postoperative) were then evaluated. Results: The median number of days requiring vasoactive drug support postoperatively was three in 234 patients, while 118 (50.4%) patients required vasoactive drug support for three days or more postoperatively. The results of the multivariate analysis indicated more preoperative colloid use (odds ratio [OR]=1.834, confidence interval [CI]:1.265-2.659, P=0.001), intraoperative use of vasoactive drug (OR=4.174, CI:1.882-9.258, P<0.001), and more postoperative crystalloid solution input per unit of body weight per day (ml/kg/d) (OR=1.087, CI:1.062-1.112, P<0.001) were risk factors for predicting postoperative hemodynamic instability. The optimal cutoff point of postoperative crystalloid use were 42.37 ml/kg/d. Conclusion: Hemodynamic instability is a key issue for consideration in the perioperative period of pheochromocytoma. The amount of preoperative colloid use, the need for intraoperative vasoactive drugs, and postoperative crystalloid solution are risk factors for predicting postoperative hemodynamic instability (registration number: ChiCT2300071166).

Long non-coding RNA EGOT is associated with 131iodine sensitivity and contributes to thyroid cancer progression by targeting miR-641/PTEN axis.

Thyroid cancer is a prevalent endocrine malignancy around the world. Radioactive 131iodine (131I) therapy is widely applied in TC patients, but the resistance affects its effectiveness in the clinics. Long non-coding RNA (lncRNA) EGOT has been reported to induce an inhibitory effect on cancer progression, but the specific function of EGOT in 131I resistance of TC cells remains unclear. Here, we successfully established 131I-resistant TC cells and evaluated the impact of EGOT on 131I resistance in the cells. Our data showed that EGOT and PTEN expression was reduced but the miR-641 expression was enhanced in 131I-resistant TC cells. EGOT inhibited viability, induced apoptosis and enhanced DNA damage in 131I-resistant TC cells. Mechanically, we identified that EGOT induced PTEN expression by targeting miR-641 in 131I-resistant TC cells. Moreover, the depletion of PTEN and miR-641 mimic reversed EGOT-relieved 131I resistance of TC cells in vitro. Thus, we conclude that lncRNA EGOT attenuated 131I resistance of TC cells by targeting miR-641/PTEN axis. The clinical functions of EGOT in TC therapy deserve to be validated in future exploration.

General anesthesia bullies the gut: a toxic relationship with dysbiosis and cognitive dysfunction.

Perioperative neurocognitive disorder (PND) is a common surgery outcome affecting up to a third of the elderly patients, and it is associated with high morbidity and increased risk for Alzheimer's disease development. PND is characterized by cognitive impairment that can manifest acutely in the form of postoperative delirium (POD) or after hospital discharge as postoperative cognitive dysfunction (POCD). Although POD and POCD are clinically distinct, their development seems to be mediated by a systemic inflammatory reaction triggered by surgical trauma that leads to dysfunction of the blood-brain barrier and facilitates the occurrence of neuroinflammation. Recent studies have suggested that the gut microbiota composition may play a pivotal role in the PND development by modulating the risk of neuroinflammation establishment. In fact, modulation of gut microbiome composition with pre- and probiotics seems to be effective for the prevention and treatment of PND in animals. Interestingly, general anesthetics seem to have major responsibility on the gut microbiota composition changes following surgery and, consequently, can be an important element in the process of PND initiation. This concept represents an important milestone for the understanding of PND pathogenesis and may unveil new opportunities for the development of preventive or mitigatory strategies against the development of these conditions. The aim of this review is to discuss how anesthetics used in general anesthesia can interact and alter the gut microbiome composition and contribute to PND development by favoring the emergence of neuroinflammation.

Impact of post-diagnosis weight change on survival outcomes in Black and White breast cancer patients.

PURPOSE: To evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients. METHODS: The study included 2888 women diagnosed with non-metastatic breast cancer in 2000-2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes. RESULTS: At diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m2 and 31.5 kg/m2 for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m2/year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88-3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91-4.86), and disease-free survival (HR = 2.12, 95% CI 1.52-2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m2/year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10-2.33 for overall survival). CONCLUSION: BMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.

Author Correction: Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Tumor-associated macrophages promote tumor metastasis via the TGF-ß/SOX9 axis in non-small cell lung cancer.

[This corrects the article DOI: 10.18632/oncotarget.21068.].

Impact of perioperative transfusion in patients undergoing resection of colorectal cancer liver metastases: A population-based study.

BACKGROUND: Perioperative allogeneic blood transfusion is associated with poorer outcomes. AIM: To identify the factors that were associated with perioperative transfusion and to examine the impact of perioperative transfusion in patients undergoing resection of colorectal cancer (CRC) liver metastases. METHODS: The United States National Inpatient Sample (NIS) database was searched for patients with CRC who received surgery for liver metastasis. Linear and logistic regression analyses were performed. RESULTS: A total of 2018 patients were included, and 480 had a perioperative transfusion. Emergency admission (adjusted odds ratio [aOR] = 1.42; 95%CI: 1.07-1.87), hepatic lobectomy (aOR = 1.76; 95%CI: 1.42-2.19), and chronic anemia (aOR = 2.62; 95%CI: 2.04-3.35) were associated with increased chances of receiving a transfusion, but receiving surgery at a teaching hospital (aOR = 0.75; 95%CI: 0.58-0.98) was associated with a decreased chance of receiving a transfusion. Receiving a perioperative transfusion was significantly associated with increased in-hospital mortality (aOR = 3.38; 95%CI: 1.57-7.25), and increased overall postoperative complications (aOR = 1.67; 95%CI: 1.31-2.13), as well as longer length of hospital stay. CONCLUSION: Patients with an emergency admission, hepatic lobectomy, chronic anemia, and who have surgery at a non-teaching hospital are more likely to receive a perioperative transfusion. Patients with CRC undergoing surgery for hepatic metastases who receive a perioperative transfusion are at a higher risk of in-hospital mortality, postoperative complications, and longer length of hospital stay.

Five Common Functional Polymorphisms in microRNAs and Susceptibility to Breast Cancer: An Updated Meta-Analysis.

AIMS: microRNAs (miRNA) play a key role in the pathogenesis of breast cancer (BC) as regulators of tumor-associated genes, and understanding their polymorphisms is critical to the control of breast carcinogenesis. Thus, the present study explored the association between five common functional polymorphisms in miRNAs (i.e., miRNA-196a2C>T, rs11614913; miRNA-146aG>C, rs2910164; miRNA-423C>A, rs6505162; miRNA-608G>C, rs4919510; miRNA-27aC>T, rs895819) and the risk of BC. MATERIALS AND METHODS: Meta-analyses were performed on 31 studies, including 14,677 BC patients and 16,143 cancer-free controls. Fourteen studies with 6147 cases and 5820 controls were analyzed for rs2910164, seventeen studies with 7021 cases and 8186 controls were analyzed for rs11614913, seven studies with 1891 (3390) cases and 2239 (5485) controls were analyzed for rs6505162 and rs4919510, respectively, and nine studies with 4499 cases and 5434 controls were analyzed for rs895819. Odds ratios (ORs) and 95% confidence intervals (CIs) were adopted to estimate BC risk. Subgroup analyses were performed for ethnicity. Because there was one study with mixed ethnicities, 16 studies were used in the analysis of Caucasian groups, and 16 studies were used for the Asian group. RESULT: Meta-analysis showed that rs895819 correlated with reduced BC risk in three genotypic models: allele (Caucasian: OR = 0.89, 95% CI = 0.82-0.97, p = 0.008; Total: OR = 0.93, 95% CI = 0.87-0.99, p = 0.03), recessive (Caucasian: OR = 0.85, 95% CI = 0.77-0.94, p = 0.002; Total: OR = 0.92, 95% CI = 0.85-0.99, p = 0.04), and dominant (Total: OR = 0.87, 95% CI = 0.77-0.99, p = 0.04). Of note, a significant publication bias for rs895819 was observed in the dominant model. Unexpectedly, the other four polymorphisms were not associated with BC risk in any of the models. CONCLUSIONS: The present study indicates that only the rs895819 polymorphism was associated with BC risk.

Tumor-associated macrophages promote tumor metastasis via the TGF-ß/SOX9 axis in non-small cell lung cancer.

Tumor-associated macrophages (TAMs), most of which display the immunosuppressive M2 phenotype, affect the tumor microenvironment and promote progression and metastasis in lung carcinoma. In this study, we analyzed clinical non-small cell lung cancer (NSCLC) samples and found that high densities of TAMs were associated with a poor prognosis in NSCLC patients. Moreover, the number of TAMs present correlated positively with expression of sex determining region Y (SRY)-related high mobility group box 9 (SOX9) in NSCLC tissues. TAMs secreted TGF-ß, which increased SOX9 expression and promoted epithelial-to-mesenchymal transition (EMT) in lung cancer cells, thereby promoting tumor proliferation, migration, and invasion. SOX9 knockdown inhibited EMT, indicating that TGF-ß-mediated EMT is SOX9-dependent. TGF-ß induced SOX9 expression by upregulating the C-jun/SMAD3 pathway. These results indicate that TGF-ß secreted by TAMs promotes SOX9 expression via the C-jun/SMAD3 pathway, thereby promoting tumor metastasis. The TGF-ß/SOX9 axis may therefore be an effective target for the treatment of lung cancer.

Distant Metastasis and Survival Outcomes after Computed Tomography-Guided Needle Biopsy in Resected Stage I-III Non-Small Cell Lung Cancer.

Background and objective Several reports describe the needle-tract implantation after percutaneous needle lung biopsy. The present study evaluated whether preoperative computed tomography-guided needle biopsy (CTNB) affected the distant metastasis and overall survival in patients with early non-small cell lung cancer (NSCLC). Methods A total of 1667 patients with pathological stage I-III NSCLC were assimilated. Of these, 168 patients received preoperative CTNB, whereas 1499 patients were not subjected to any biopsy before surgical resection. Propensity score matching method was adopted to balance the observed covariates between the two groups. Cox regression analysis and Kaplan-Meier estimations were used for survival analysis. Subset analysis was performed in the p-stage ≤ II cases. Results The distant metastasis and mortality were not significantly increased for all patients with preoperative CTNB (P = 0.142 and P = 0.125, respectively). The subset analysis of p-stage ≤ II cases showed that CTNB increased the risk of distant metastasis (P = 0.032) while not increasing the risk of mortality (P = 0.086). Conclusion CTNB can increase the risk of distant metastasis in the p-stage ≤ II patients.

Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/ß-catenin signalling pathway.

Infiltration of macrophages plays a critical role in the connection between inflammation and cancer invasion; however, the molecular mechanism that enables this crosstalk remains unclear. This paper investigates a molecular link between infiltration of macrophages and metastasis of lung cancer cells. In this study, the macrophage density and cyclooxygenase-2 (COX-2) protein were examined in surgical specimens by immunohistochemistry (IHC), and the prostaglandin E2 (PGE2) levels were determined in the blood of 30 non-small cell lung cancer (NSCLC) patients using enzyme-linked immunosorbent assay (ELISA). We demonstrated that macrophage infiltration was significantly associated with elevated tumour COX-2 expression and serum PGE2 levels in NSCLC patients. Interestingly, the COX-2 and PGE2 levels as well as macrophages were poor predictors of NSCLC patient survival. THP-1-derived macrophages were co-cultured in vitro with A549 and H1299 lung cancer cells. In the co-culture process, interleukin-6 (IL-6) induced the COX-2/PGE2 pathway in lung cancer cells, which subsequently promoted ß-catenin translocation from the cytoplasm to the nucleus, resulting in epithelial-mesenchymal transition (EMT) and lung cancer cell invasion. Our findings show that the IL-6-dependent COX-2/PGE2 pathway induces EMT to promote invasion of tumour cells through ß-catenin activation during the interaction between macrophages and lung cancer cells, which suggests that inhibition of COX-2/PGE2 or macrophages has the potential to suppress metastasis of lung cancer cells.

Luffa echinata Roxb. Induced Apoptosis in Human Colon Cancer Cell (SW-480) in the Caspase-dependent Manner and Through a Mitochondrial Apoptosis Pathway.

BACKGROUND: Luffa echinata Roxb. (LER) (Cucurbitaceae) showed tremendous medicinal importance and are being used for the treatment of different ailments. OBJECTIVE: In this study, the antiproliferative properties and cell death mechanism induced by the extract of the fruits of LER were investigated. MATERIALS AND METHODS: MTT and LDH assay were used to test the antiproliferative and cytotoxicity of LER extract, respectively. The intracellular ROS were measured by a fluorometric assay. The expression of several apoptotic-related proteins in SW-480 cells treated by LER was evaluated by Western blot analysis. RESULTS: The methanolic extract of LER fruits inhibited the proliferation of human colon cancer cells (SW-480) in both dose- and time-dependent manners. The LER-treated cells showed obvious characteristics of cell apoptosis, including cell shrinkage, destruction of the monolayer, and condensed chromatin. In addition, treatments of various concentrations of LER extracts caused the release of lactate dehydrogenase as a dose-dependent manner via stimulation of the intracellular metabolic system. LER induced apoptosis, DNA fragmentation, and cellular ROS accumulation in SW-480 cells. Treatment of LER on SW-480 cells promoted the expression of caspases, Bax, Bad, and p53 proteins and decreased the levels of Bcl-2 and Bcl-XL. CONCLUSIONS: These results indicated that treatment with LER-induced cell death in mitochondrial apoptosis pathway by regulating pro-apoptotic proteins via the up regulation of the p53 protein. These findings highlight the potentials of LER in the treatment of human colon cancer. SUMMARY: LER induced apoptosis, DNA fragmentation, and cellular ROS accumulation in SW-480 cells. Treatment of LER on SW-480 cells promoted the expression of caspases, Bax, Bad, and p53 proteins and decreased the levels of Bcl-2 and Bcl-XL.

Interleukin-17 promotes angiogenesis by stimulating VEGF production of cancer cells via the STAT3/GIV signaling pathway in non-small-cell lung cancer.

The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.

Interleukin-17 levels correlate with poor prognosis and vascular endothelial growth factor concentration in the serum of patients with non-small cell lung cancer.

OBJECTIVE: The aim of this study was to explore the clinical role of serum interleukin-17 in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHOD: IL-17 expression and microvessel density (MVD) were measured via immunohistochemistry in 58 NSCLC tissues. Serum IL-17 and VEGF levels in NSCLC patients (n = 43) and healthy controls (n = 37) were analyzed via enzyme-linked immunosorbent assay. RESULTS: Serum IL-17 was elevated and the levels positively correlated with VEGF concentration in NSCLC patients. Multivariate analyses revealed that serum IL-17 levels were an independent prognostic factor in NSCLC. CONCLUSION: IL-17 may play a role in NSCLC progression by promoting angiogenesis.

Newly identified biomarkers for detecting circulating tumor cells in lung adenocarcinoma.

Circulating tumor cells (CTCs) have been implicated in cancer prognosis and follow up. Detection of CTCs was considered significant in cancer evaluation. However, due to the heterogeneity and rareness of CTCs, detecting them with a single maker is usually challenged with low specificity and sensitivity. Previous studies concerning CTCs detection in lung cancer mainly focused on non-small cell lung carcinoma. Currently, there is no report yet describing the CTC detection with multiple markers in lung adenocarcinoma. In this study, by employing quantitative real-time PCR, we identified four candidate genes (mRNA) that were significantly elevated in peripheral blood mononuclear cells and biopsy tissue samples from patients with lung adenocarcinoma: cytokeratin 7 (CK7), Ca(2+)-activated chloride channel-2 (CLCA2), hyaluronan-mediated motility receptor (HMMR), and human telomerase catalytic subunit (hTERT). Then, the four markers were used for CTC detection; namely, positive detection was defined if at least one of the four markers was elevated. The positive CTC detection rate was 74.0% in patients with lung adenocarcinoma while 2.2% for healthy controls, 6.3% for benign lung disease, and 48.0% for non-adenocarcinoma non-small cell lung carcinoma. Furthermore, in a three-year follow-up study, patients with an increase in the detection markers of CTCs (CK7, CLCA2, HMMR or hTERT) on day 90 after first detection had shorter survival time compared to those with a decrease. These results demonstrate that the combination of the four markers with specificity and sensitivity is of great value in lung adenocarcinoma prognosis and follow up.

Combination of four gene markers to detect circulating tumor cells in the peripheral blood of patients with advanced lung adenocarcinoma using real-time PCR.

The aim of this study was to establish a robust and reliable assay for the detection of circulating tumor cells (CTCs) in the peripheral blood (PB) of patients with advanced lung adenocarcinoma. We used real-time reverse transcription PCR (RT-PCR) to detect survivin, human telomerase reverse transcriptase (hTERT), cytokeratin-7 (CK-7) and thyroid transcription factor 1 (TTF-1) mRNA expression levels in 68 advanced lung adenocarcinoma patients and 30 healthy patients. Statistical analyses were additionally performed to examine the correlation between the mRNA expression levels of these markers with the clinicopathological features of advanced lung adenocarcinoma patients. The sensitivity of these four mRNA markers in the PB of advanced lung adenocarcinoma patients was 41.18, 61.76, 41.18 and 35.29%, respectively. The sensitivity of these four markers combined was 82.35%, which was significantly higher compared with single marker detection. Statistical analysis demonstrated that high expression levels of survivin, hTERT and TTF-1 mRNA are positively correlated with lymph node classification, and high expression levels of survivin, hTERT, CK7 and TTF-1 mRNA are positively correlated with distant metastasis (P<0.05). In addition, overexpression of these four mRNA markers is positively correlated with disease progression (P<0.05). Our data suggest that the combination of survivin, hTERT, CK-7 and TTF-1 mRNA markers may provide a valuable tool for CTC detection and is associated with disease progression in advanced lung adenocarcinoma patients.

A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer.

BACKGROUND: Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer (NSCLC) patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with different ERCC1 C118T/ MDR1 C3435T single-nucleotide polymorphism (SNP). METHODS: Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. RESULTS: A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 C118T, test for heterogeneity was done (χ(2) = 13.41, P = 0.1), and the odds ratio (OR) for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 (95% CI 1.09 - 2.06, P = 0.01). In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done (χ(2) = 3.22, P = 0.36), and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 (95% CI 1.44 - 3.68, P = 0.0005). CONCLUSIONS: The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 C118T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

Luffa echinata Roxb. induces human colon cancer cell (HT-29) death by triggering the mitochondrial apoptosis pathway.

The antiproliferative properties and cell death mechanism induced by the extract of the fruits of Luffa echinata Roxb. (LER) were investigated. The methanolic extract of LER inhibited the proliferation of human colon cancer cells (HT-29) in both dose-dependent and time-dependent manners and caused a significant increase in the population of apoptotic cells. In addition, obvious shrinkage and destruction of the monolayer were observed in LER-treated cells, but not in untreated cells. Analysis of the cell cycle after treatment of HT-29 cells with various concentrations indicated that LER extracts inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle. The Reactive oxygen species (ROS) level determination revealed that LER extracts induced apoptotic cell death via ROS generation. In addition, LER treatment led to a rapid drop in mitochondrial membrane potential (MMP) as a decrease in fluorescence. The transcripts of several apoptosis-related genes were investigated by RT-PCR analysis. The caspase-3 transcripts of HT-29 cells significantly accumulated and the level of Bcl-XL mRNA was decreased after treatment with LER extract. Furthermore, the ratio of mitochondria-dependent apoptosis genes (Bax and Bcl-2) was sharply increased from 1.6 to 54.1. These experiments suggest that LER has anticancer properties via inducing the apoptosis in colon cancer cells, which provided the impetus for further studies on the therapeutic potential of LER against human colon carcinoma.