Association between inflammatory factors and melanoma: a bidirectional Mendelian randomization study.

PURPOSE: This study performed a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein and 41 inflammatory regulators with melanoma, including data from UK Biobank, Cardiovascular Risk in Young Finns Study, and Cohorts for Inflammation Work Group. METHODS: We selected the inverse variance weighting (IVW) to merge the estimated causal effects of multiple SNPs into a weighted average. To evaluate the heterogeneities of IVW, the Cochran Q statistic, and I2 index were used. What's more, several sensitivity analyses were employed, including IVW, MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO). RESULTS: With SNPs reaching P < 5 × 10-8, the analyses findings revealed that IL-16 had a significant positively association with genetically risk of melanoma (ORIVW: 1.05; 95% CI: 1.03-1.07; P < 0.001), and high levels of MCP1 (ORIVW: 1.13; 95% CI: 1.03-1.23; P = 0.01) were suggestively associated with melanoma susceptibility. What's more, TNF-ß (ORIVW: 1.07; 95% CI: 1.01-1.13; P = 0.02) and IL-8 (ORIVW: 1.08, 95% CI: 1.01-1.16; P = 0.03) were demonstrated a positive association with the risk of melanoma under a less stringent cut-off (P < 5 × 10-6). Conversely, we found a facilitative effect of melanoma susceptibility on IP-10 and inhibitory effects on IL-6, IL-1b, and GRO-α. CONCLUSION: The genetic evidence that we have uncovered indicates a potential association between the levels of specific inflammatory markers (IL-16, IL-8, MCP-1, and TNF-ß) and the risk of melanoma. Further research is imperative to translate these findings into clinical applications.

Berberine: Potential preventive and therapeutic strategies for human colorectal cancer.

Colorectal cancer (CRC) is a common digestive tract tumor, with incidences continuing to rise. Although modern medicine has extended the survival time of CRC patients, its adverse effects and the financial burden cannot be ignored. CRC is a multi-step process and can be caused by the disturbance of gut microbiome and chronic inflammation's stimulation. Additionally, the presence of precancerous lesions is also a risk factor for CRC. Consequently, scientists are increasingly interested in identifying multi-target, safe, and economical herbal medicine and natural products. This paper summarizes berberine's (BBR) regulatory mechanisms in the occurrence and development of CRC. The findings indicate that BBR regulates gut microbiome homeostasis and controls mucosal inflammation to prevent CRC. In the CRC stage, BBR inhibits cell proliferation, invasion, and metastasis, blocks the cell cycle, induces cell apoptosis, regulates cell metabolism, inhibits angiogenesis, and enhances chemosensitivity. BBR plays a role in the overall management of CRC. Therefore, using BBR as an adjunct to CRC prevention and treatment could become a future trend in oncology.

Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition.

As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer (CRC) remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in CRC. Bioinformatics analysis in specimens from CRC patients and expression analysis in CRC cell lines showed that POU4F2 was upregulated at the mRNA and protein levels in CRC. Depletion of POU4F2 suppressed the metastatic phenotypes of CRC cells, including cell migration, invasion, and the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, depletion of POU4F2 decreased the number of lung metastatic nodes in nude mice. Mechanistically, POU4F2 positively regulated the Hedgehog signaling pathway, as inferred from the downregulation of the expression of sonic Hedgehog homolog, patched 1, Smoothened, and GLI family zinc finger 1 in vitro and vivo following silencing of POU4F2. Furthermore, the SMO agonist SAG reversed the effects of POU4F2 knockdown in CRC. Functionally, POU4F2 contributed to the Hedgehog signaling-regulated activation of the EMT process and promotion of CRC cell migration and invasion. Collectively, these findings elucidated the role of POU4F2 as a tumor promotor in CRC through the regulation of Hedgehog signaling-mediated EMT and suggested that POU4F2 suppression might be a promising therapeutic target in inhibiting CRC metastasis.

p-MEK expression predicts prognosis of patients with adenocarcinoma of esophagogastric junction (AEG) and plays a role in anti-AEG efficacy of Huaier.

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.

Impact of chemotherapy and radiotherapy on the survival of elderly esophageal cancer patients undergoing surgery: a SEER database analysis.

BACKGROUND: Esophageal cancer (EC) is a common and lethal carcinoma; however, the effectiveness and feasibility of the chemo- and radio-therapy (CRT) for the elderly patients (≥ 70 years) with surgery have not been fully discussed. The purpose of this study was to investigate the potential effect of CRT on the prognosis. METHODS: A total of 1085 patients (534 CRT patients vs. 551 non-CRT patients) from 1998 to 2016 were collected from the Surveillance, Epidemiology, and End Results database according to the inclusion and exclusion criteria. Using the competing risk regression and survival analysis, an overall estimation of the effectiveness of CRT was performed on a well-balanced cohort via performing propensity score matching. Then, the specific impact of CRT on high- (n = 557) and low-risk (n = 528) cohorts derived from the nomogram's risk quantification for every patient were further evaluated respectively. Additionally, the advantages of the nomogram model and the conventional tumor, node, metastasis (TNM, 6th revision) staging system were compared. RESULTS: A better survival outcome was observed among patients receiving both surgery and CRT than those who underwent surgery alone (HR: 0.55, 95% CI 0.45-0.68, P < 0.001), especially for those with tumors characterized by poor differentiation, large tumor size, advanced T staging, lymphatic metastasis, and distant metastasis (HR: 0.48, 95% CI 0.39-0.59, P < 0.001), while no benefit was observed among the low-risk patients. Furthermore, the newly established nomogram model might be better than the TNM (6th revision) staging system but more data needed. CONCLUSION: Aggressive treatments, such as surgery, chemotherapy, and radiotherapy, were considered effective for selected elderly patients with EC according to the newly established nomogram model.

A Predictive Nomogram for Early Mortality in Stage IV Gastric Cancer.

BACKGROUND The study was intended to establish predictive nomogram models for predicting total early mortality (the probability of surviving less than or equal to 3 months) and cancer-specific early mortality in patients with stage IV gastric cancer. This was the first study to establish prognostic survival in patients with stage IV gastric cancer. MATERIAL AND METHODS Patients from the SEER database were identified using inclusion and exclusion criteria. Their clinical characteristics were statistically analyzed. The Kaplan-Meier method and the log-rank test were used to compare the influences of different factors on survival time. Logistic regression models were conducted to explore the correlative factors of early mortality. A nomogram was established based on factors significant in the logistic regression model and an internal validation was performed. RESULTS Of the 11,036 eligible patients included in the study, 4932(44.7%) patients resulted in total early death (42.6% died of the cancer and 2.1% died of other reasons). Larger tumor size, poor differentiation, and liver metastasis were positively related to cancer-specific early mortality. Surgery was negatively related to total early mortality and cancer-specific early mortality, while cardia was only negatively associated with total early death. Predictive nomogram models for total early mortality and cancer-specific early mortality have been validated internally. The areas under the receiver operating characteristics curve were 73.5%, and 68.0%, respectively, and the decision curve analysis also proved the value of the models. CONCLUSIONS The nomogram models proved to be a suitable tool for predicting the early mortality in stage IV gastric cancer.

Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5 cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5 cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5 cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5 cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

Expression of Protein 4.1 Family in Breast Cancer: Database Mining for 4.1 Family Members in Malignancies.

BACKGROUND The protein 4.1 family is a family of cytoskeletal proteins that play an important role in maintaining normal cell morphology and cell adhesion, migration, division, and intercellular signaling. The main aim of this study was to explore the prognostic significance of the protein 4.1 family in breast cancer (BC) patients and to provide new biomarkers and therapeutic targets for the diagnosis and treatment of BC. MATERIAL AND METHODS The expression of 4.1 family members in various tumor types was compared to normal controls using the ONCOMINE and GOBO databases. The prognostic significance of the 4.1 family in BC patients was determined by Kaplan-Meier Plotter. RESULTS EPB41L2 (4.1G) was expressed at higher levels in normal tissues compared with BC patients for all 4.1 family members. In survival analysis, 4.1G and EPB41 (4.1R) mRNA high expressions were associated with better survival in BC patients. Moreover, 4.1G high expression was significantly associated with longer overall survival (OS) in luminal A and protracted relapse-free survival (RFS) in luminal B subtype BC patients who received Tamoxifen treatment. In addition, high expression of each 4.1 family member also showed better prognostic value in different molecular subtypes of BC. CONCLUSIONS These results indicate that the protein 4.1 family can be regarded as novel biomarkers and potential therapeutic targets for BC. Further research is needed to explore the detailed biological functions.

Mesenchymal stem cell-derived exosomes as delivery vehicles for non-coding RNAs in lung diseases.

The burden of lung diseases is gradually increasing with an increase in the average human life expectancy. Therefore, it is necessary to identify effective methods to treat lung diseases and reduce their social burden. Currently, an increasing number of studies focus on the role of mesenchymal stem cell-derived exosomes (MSC-Exos) as a cell-free therapy in lung diseases. They show great potential for application to lung diseases as a more stable and safer option than traditional cell therapies. MSC-Exos are rich in various substances, including proteins, nucleic acids, and DNA. Delivery of Non-coding RNAs (ncRNAs) enables MSC-Exos to communicate with target cells. MSC-Exos significantly inhibit inflammatory factors, reduce oxidative stress, promote normal lung cell proliferation, and reduce apoptosis by delivering ncRNAs. Moreover, MSC-Exos carrying specific ncRNAs affect the proliferation, invasion, and migration of lung cancer cells, thereby playing a role in managing lung cancer. The detailed mechanisms of MSC-Exos in the clinical treatment of lung disease were explored by developing standardized culture, isolation, purification, and administration strategies. In summary, MSC-Exo-based delivery methods have important application prospects for treating lung diseases.

Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Several recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies. METHODS: A meta-analysis of prospective/retrospective cohort studies was conducted to compare the prognosis of preoperatively genetically positive and genetically negative NSCLC patients. The endpoints used in the included studies were overall survival (OS) and recurrence-free survival (RFS). The objective of the meta-analysis was to comprehensively explore the prognostic value of preoperative ctDNA for patients with non-small-cell lung cancer (NSCLC) and its significance in guiding postoperative adjuvant therapy (AT) in patients with NSCLC. RESULTS: The preliminary analysis identified 1565 studies, among which only 11 studies fulfilled the eligibility criteria and were finally included in the present systematic review and meta-analysis. The statistical results revealed that the expression of preoperative ctDNA was associated with worse RFS (HR = 3.00; 95% CI 2.26-3.98; I2 = 0%) and OS (HR = 2.77; 95% CI 1.67-4.58; I2 = 0%), particularly in lung adenocarcinoma (LUAD) patients (RFS: HR = 3.46; 95% CI 2.37-5.05; I2 = 0%; OS: HR = 3.52; 95% CI 1.91-6.49; I2 = 0%) and patients with I-II stage of NSCLC (RFS: HR = 2.84; 95% CI 1.88-4.29; I2 = 0%; OS: HR = 2.60; 95% CI 1.43-4.74; I2 = 0%). Moreover, compared to patients with negative preoperative ctDNA, patients with positive preoperative ctDNA presented greater survival benefits (HR = 0.39; 95% CI 0.22-0.67; I2 = 2%) from postoperative AT. CONCLUSION: The evaluation of the prognostic value of preoperative ctDNA revealed that preoperative ctDNA might be used as a prognostic biomarker for patients with LUAD or those with stage I-II NSCLC. In addition, postoperative AT is recommended for NSCLC patients with positive preoperative ctDNA, regardless of the disease stage and subtype.

Efficacy and safety of neoadjuvant combination immunotherapy in surgically resectable malignant solid tumors: a systematic review and meta-analysis.

OBJECTIVES: Neoadjuvant immunotherapy has emerged as a prominent research focus recently. For potentially operable patients, neoadjuvant therapy serves as a primary method to reduce tumor load and facilitate surgical interventions. METHODS: We retrieved articles from PubMed, Embase, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology websites from inception to December 2023. Statistical analyses were performed using the R software. Primary outcomes assessed included major pathological response (MPR), pathological complete response (pCR), and treatment-related adverse events (trAEs). RESULTS: 29 studies encompassing 1163 patients were included. The MPR rate of neoadjuvant combination immunotherapy was 38% (95% confidence interval [CI]: 25%-52%), and the pCR rate was 33% (95%CI: 25%-42%). These values were significantly higher than those obtained with single agent immunotherapy (p < 0.001). The pooled incidence of overall trAEs was 83% (95%CI: 73%-92%), and grade (G) 3-4 trAEs was 22% (95%CI: 15%-29%), both significantly higher than those observed with single agent immunotherapy (p < 0.05). CONCLUSION: This study demonstrated the efficacy of neoadjuvant combination immunotherapy. Given that the majority of the included trials were phase II with small sample sizes, further multicenter phase III randomized controlled trials should be conducted to validate the findings of the review.

Association between human blood metabolome and the risk of gastrointestinal tumors.

BACKGROUND: The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer). METHODS: We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions. RESULTS: We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors. CONCLUSIONS: The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.

Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy.

Background: Renal cell carcinoma (RCC) is the most common renal malignancy, and may metastasize to different sites in the body via hematogenous and lymphomatous routes. The pancreas is a rare metastatic site of metastatic RCC (mRCC) and isolated pancreatic metastasis of RCC (isPMRCC) is even rarer. Results: The present report describes a case of isPMRCC that recurred 16 years after surgery. The patient responded well to the treatment with pancreaticoduodenectomy and systemic therapy, and no recurrence was recorded after 2 years. Conclusions: isPMRCC is a distinct subgroup of RCC with unique clinical characteristics that may be explained by its underlying molecular mechanisms. Surgery and systemic therapy confer survival benefits to patients with isPMRCCs, although the recurrence problem has to be paid attention to.

Predictors of Distant Metastasis and Prognosis in Newly Diagnosed T1 Intrahepatic Cholangiocarcinoma.

Background: According to American Joint Committee on Cancer (AJCC) 8th staging system, T1 intrahepatic cholangiocarcinoma (T1 ICC) is considered a tumor with no vascular invasion. However, T1 ICC usually occurs distant metastasis (DM), and the clinical features of these patients could help clinicians identify the high-risk population. Methods: We reviewed 1959 newly diagnosed patients with T1 ICC from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2018. Logistic regression models and Cox proportional hazards models were conducted to predict the risk of DM and overall survival (OS), respectively, and then, web-based nomograms were constructed. Decision curve analysis (DCA) and clinical impact curves (CIC) were used to measure the clinical utility of the models. The low-, medium-, and high-risk groups were identified by calculating the summary of the risk points. Nomograms on the web were also created to help clinicians better use these prediction models. Results: Tumor size and lymph node metastasis accounted for the first two largest proportions among the DM nomogram scores, while surgery, DM, age at diagnosis, chemotherapy, and lymph node metastasis occupied the largest percentage in OS nomogram. DM nomogram was established for these newly diagnosed patients with T1 ICC, and OS nomogram was developed to visually predict the OS rate of 3, 5, and 10 years. The calibration curves revealed a valid predictive accuracy of nomograms, of which the C-index was 0.703 and 0.740, respectively, for good discrimination. DCAs, CICs, and risk subgroups showed the clinical validity of these nomograms. Two websites were created to make it easier to use these nomograms. Conclusions: Novel web-based nomograms predicting the risk of DM and OS for T1 ICC were constructed. These predictive tools might help clinicians make precise clinical strategies for each patient with T1 ICC.

Prognostic value of postoperative ctDNA detection in patients with early non-small cell lung cancer: a systematic review and meta-analysis.

Background: Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for monitoring early non-small cell lung cancer (ENSCLC), particularly after radical surgery. However, the prognostic value of postoperative ctDNA is still being investigated due to the small sample size and heterogeneity of patients with ENSCLC in current trials. Moreover, the potential clinical utility of ctDNA assessment for administering adjuvant therapy (AT) in patients with ENSCLC is also an important area of active research. Objectives: We aimed to identify the prognostic value of postoperative ctDNA detection in ENSCLC patients with stages I-III. Design: This study type is a systematic review and meta-analysis. Data sources and methods: We conducted a search in the Cochrane Library, Embase, PubMed, and ScienceDirect for prospective or retrospective investigations involving patients with ENSCLC, gathering outcomes based on predefined end points. The literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the Newcastle-Ottawa scale was employed to carry out a quality evaluation of the included studies. The primary end point of the study was to evaluate the association of ctDNA status in two time points (within 1 month after surgery and long-term postoperative monitoring with more than 3 months) with relapse-free survival (RFS) and overall survival (OS). In addition, the study investigated the role of ctDNA in predicting the response to AT. The secondary end points of the study were to determine the impact of ctDNA on RFS and OS in different subgroups of ENSCLC patients based on pathological subtypes and TNM staging. Results: In total, 2149 studies were screened, and 11 studies met the inclusion criteria for the analysis. The presence of ctDNA within 1 month after surgery as well as long-term postoperative ctDNA were both associated with poorer RFS [hazard ratio (HR) = 4.43; 95% CI: 3.23-6.07 and HR = 7.99; 95% CI: 3.28-19.44, respectively] and worse OS (HR = 5.07; 95% CI: 2.80-9.19 and HR = 7.49; 95% CI: 3.42-16.43, respectively). Most subgroup analyses yielded similar results. Moreover, ctDNA-positive patients could acquire survival benefits from AT (HR = 0.30; 95% CI: 0.16-0.54), while ctDNA-negative patients that received AT did not show significant improvement in RFS (HR = 1.18; 95% CI: 0.67-2.09). Conclusion: The postoperative ctDNA assessment is a promising approach to stratify the risk of relapse and death in ENSCLC patients. Our data suggest that patients with negative ctDNA in the postoperative setting may not benefit from AT, which warrants further investigation. This finding, if validated in prospective trials with a larger sample size, could aid in better-individualized treatment for patients and avoid potential side effects of AT. Registration: This study was designed in accordance with PRISMA and registered with PROSPERO (CRD42022311615).

Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis.

Background: Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Results: Sixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. Conclusion: This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

Survival analysis of age-related oral squamous cell carcinoma: a population study based on SEER.

BACKGROUND: This research aimed to investigate the prognostic factors of oral squamous cell carcinoma (OSCC), especially the role of age. METHODS: A total of 33,619 cases of OSCC were received from the Surveillance, Epidemiology, and End Results (SEER) database during 2005-2015. Kaplan-Meier curves of 5-year overall survival rates and 5-year cancer-specific survival rates were performed, and univariate and multivariate Cox regression analyses as well as competing risk model were used to help understand the relationship between various factors and mortality of OSCC. RESULTS: Compared to 18-39-year-old group, the older age was an important predictor of worse prognosis. The multivariate analysis of overall survival (OS) was 50-59 years (HR, 1.32; 95% CI 1.17-1.48; p ≤ .001), 60-69 years (HR, 1.66; 95% CI 1.42-1.87; p ≤ .001) and 70 + years (HR, 3.21; 95% CI 2.86-3.62; p ≤ .001), respectively, while the specific value of competing risk model was 60-69 years (HR, 1.21; 95% CI 1.07-1.38; p = .002) and 70 + years (HR, 1.85; 95% CI 1.63-2.10; p ≤ .001). In addition, female gender, unmarried, Blacks, tumor in floor of mouth, size and higher Tumor Node Metastasis (TNM) classification were also other predictors that signify significant clinically deterioration of OS/cancer-specific survival (CSS). CONCLUSIONS: Our research revealed that age was an important factor in explaining the difference of survival in the whole process of OSCC. It is suggested that we should pay attention to the influence of age on diagnosis, treatment and prognosis in the clinical process.

Nomograms for Predicting Specific Distant Metastatic Sites and Overall Survival of Breast Invasive Ductal Carcinoma Patients After Surgery: A Large Population-Based Study.

Background: Breast cancer (BC) has become the most common malignancy worldwide, accounting for 11.7% of newly diagnosed cancer cases last year. Invasive ductal carcinoma (IDC) is the most common pathological type of BC. However, there were few studies to predict distant metastatic sites and overall survival (OS) of IDC patients. Methods: Post-operative IDC patients from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Nomograms were developed to predict the specific distant metastatic sites and OS of IDC patients. The performance of nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of IDC patients with distant metastases. Results: A total of 171,967 post-operative IDC patients were enrolled in our study. Univariate and multivariate analyses were used to establish the nomograms of significant variables. The AUC of the nomograms for the prediction of liver, lung, bone, and brain metastases was 0.903, 0.877, 0.863, and 0.811, respectively. In addition, the AUC of the nomogram for the prediction of 1-, 3-, and 5-year OS was 0.809, 0.813, 0.787, respectively. Calibration curves and DCA showed good consistency and clinical benefits, respectively. Conclusions: We constructed new predictive models for liver, lung, brain, bone metastases and 1-, 3-, and 5-year OS in IDC patients. These can help clinicians to individualize the treatment of IDC patients, so that patients can get the more appropriate treatment options.

The antitumor properties of atractylenolides: Molecular mechanisms and signaling pathways.

Drugs that exhibit a high degree of tumor cell selectivity while minimizing normal cell toxicity are an area of active research interest as a means of designing novel antitumor agents. The pharmacological benefits of Chinese herbal medicine-based treatments have been the focus of growing research interest in recent years. Sesquiterpenoids derived from the Atractylodes macrocephala volatile oil preparations exhibit in vitro and in vivo antitumor activity. Atracylenolides exhibit anti-proliferative, anti-metastatic, and immunomodulatory activity in a range of tumor cell lines in addition to being capable of regulating metabolic activity such that it is a promising candidate drug for the treatment of diverse cancers. The present review provides a summary of recent advances in Atractylenolide-focused antitumor research efforts.