Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Cholangiocarcinomas(bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic,perihilar and extrahepatic bile ducts.Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management.First of all,it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients.Overall,cholangiocarcinomas have a very poor prognosis.The 5 year survival rate is 5%-10%.In cases with a potentially curative surgery,5 year survival rates of 25%-30% are reported.Therefore,it is necessary to increase the cure rate from surgery,exploring the survival benefit of any adjuvant strategy.It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas.There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined.The most relevant studies in the adjuvant setting are one from Japan,the well known ESPAC-3 and BILCAP from the United Kingdom and a meta-analysis.We show the results of these trials.According to medical oncology guidelines,postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins,as well as for those with a complete resection but node-positive disease.Clinical trials are ongoing.The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients:(1) patients who have had surgery but with macroscopic residual disease;(2) patients with locally recurrent disease after potentially curative treatment;and(3) patients with locally unresectable disease at presentation.In these patients,surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local tumor effects.Nowadays,no neoadjuvant therapy can be considered a standard approa

为 cholangiocarcinoma 的化疗: 更改

Trp53R172H and kmsg12d cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify the patient subsets most likely to experience meaningful benefit from this important class of agents.

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The Role of Angiogenesis in Hepatocellular Carcinoma.

Most genetic information is expressed as, and transacted by, proteins. Yet, less than 2% of the human genome actually codes for proteins, prompting a search for functions for the other 98% of the genome, once considered to be mostly “junk DNA.” Transcription is pervasive, however, and high-throughput sequencing has identified tens of thousands of distinct RNAs generated from the non—protein—coding portion of the genome ( 1 ). These so-called noncoding RNAs vary in length, but like protein-coding RNAs, appear to be linear molecules with 5′ and 3′ termini, reflecting the defined start and end points of RNA polymerase on the DNA template. But do all RNAs have to be linear?

A Circuitous Route to Noncoding RNA

It has been reported that there are multiple mechanisms by which bufalin could exert its antimetastatic effect. HIF-1α has been reported to be involved in tumor migration and invasion by regulating EMT. However, it is not known whether bufalin could exert the antimetastatic effect by modulating HIF-1α expression in hepatocellular carcinoma. In the present study, we aimed to evaluate the antimetastatic potential of bufalin in vivo and in vitro. Our results demonstrated that the liver/lung metastases were significantly reduced in bufalin-treated mice, as tested in the orthotopic transplanted and tail vein injection tumor models. Furthermore, the epithelial-to-mesenchymal transition (EMT) was inhibited in bufalin-treated tumors, as reflected the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, Snail. Similar results were observed in SMMC7721 cells treated with bufalin. Moreover, the transforming growth factor-β1 (TGF-β1)-induced EMT was also abrogated by bufalin. Mechanistically, our study demonstrated that hypoxia-inducible factor-1α (HIF-1α) played an important role in the antimetastatic effect of bufalin in hepatocellular carcinoma. Importantly, HIF-1α expression may be regulated through the inhibition of the PI3K/AKT/mTOR pathway. Taken together, our results suggest that bufalin suppresses hepatic tumor invasion and metastasis and that this process may be related to the PI3K/AKT/mTOR/ HIF-1α axis.

/pdf/bufalin-suppresses-hepatocellular-carcinoma-invasion-and-1hurw9mqrh.pdf

Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1α via the PI3K/AKT/mTOR pathway

Importance Information about stage of cancer at diagnosis, use of therapy, and survival among patients from different racial/ethnic groups with 1 of the most common cancers is lacking. Objective To assess stage of cancer at diagnosis, use of therapy, overall survival (OS), and cancer-specific survival (CSS) in patients with cancer from different racial/ethnic groups. Design, Setting, and Participants This cohort study included 950 377 Asian, black, white, and Hispanic patients who were diagnosed with prostate, ovarian, breast, stomach, pancreatic, lung, liver, esophageal, or colorectal cancers from January 2004 to December 2010. Data were collected using the Surveillance, Epidemiology, and End Results (SEER) database, and patients were observed for more than 5 years. Data analysis was conducted in July 2018. Main Outcomes and Measures Multivariable logistic and Cox regression were used to evaluate the differences in stage of cancer at diagnosis, treatment, and survival among patients from different racial/ethnic groups. Results A total of 950 377 patients (499 070 [52.5%] men) were included in the study, with 681 251 white patients (71.7%; mean [SD] age, 65 [12] years), 116 015 black patients (12.2%; mean [SD] age, 62 [12] years), 65 718 Asian patients (6.9%; mean [SD] age, 63 [13] years), and 87 393 Hispanic patients (9.2%; mean [SD] age, 61 [13] years). Compared with Asian patients, black patients were more likely to have metastatic disease at diagnosis (odds ratio [OR], 1.144; 95% CI, 1.109-1.180;P  Conclusions and Relevance In this study of patients with 1 of 9 leading cancers, stage at diagnosis, treatment, and survival were different by race and ethnicity. These findings may help to optimize treatment and improve outcomes.

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Differences in Stage of Cancer at Diagnosis, Treatment, and Survival by Race and Ethnicity Among Leading Cancer Types.

Long non-coding RNA LINC00346 has been recently suggested as a prognostic marker in pancreatic cancer. However, its biological function in pancreatic cancer has not yet been determined. In this study, we attempted to ascertain the role of LINC00346 in regulating the aggressiveness of pancreatic cancer. The effects of overexpression and knockdown of LINC00346 on the proliferation, cell cycle progression, apoptosis, and gemcitabine resistance were investigated. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were performed to search for potential microRNAs (miRs) that can interact with LINC00346. Overexpression of LINC00346 significantly enhanced the proliferation, colony formation, and tumorigenesis of pancreatic cancer cells. Conversely, knockdown of LINC00346 suppressed pancreatic cancer cell proliferation and caused a cell-cycle arrest at the G2/M-phase. Depletion of LINC00346 also enhanced gemcitabine sensitivity in pancreatic cancer cells both in vitro and in vivo. Mechanistic investigation revealed that LINC00346 acted as a sponge for miR-188-3p and blocked the repression of BRD4 by miR-188-3p in pancreatic cancer cells. Clinical evidence indicated a negative correlation between LINC00346 and miR-188-3p in pancreatic cancer specimens. Rescue experiments showed that LINC00346 attenuated the growth-suppressing and chemosensitizing effects of miR-188-3p on pancreatic cancer cells. In addition, silencing of BRD4 significantly inhibited LINC00346-induced pancreatic cancer cell proliferation and colony formation. LINC00346 shows the ability to promote pancreatic cancer growth and gemcitabine resistance, which is in part mediated by antagonization of miR-188-3p and induction of BRD4. Targeting LINC00346 may improve gemcitabine-based therapeutic efficacy.

/pdf/long-non-coding-rna-linc00346-promotes-pancreatic-cancer-2jlgl66a04.pdf

Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression.

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P 0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

Establishing a prognostic genetic signature closely related to the tumor immune microenvironment (TIME) to predict clinical outcomes is necessary. Using the Gene Expression Omnibus (GEO) database of a non‑small cell lung cancer (NSCLC) cohort and the immune score derived from the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, we applied the least absolute shrinkage and selection operator (LASSO) Cox regression model to screen a 10‑gene signature among the 448 differentially expressed genes and found that the risk prediction models constructed by 10 genes could be more sensitive to prognosis than TNM (Tumor, Lymph node and Metastasis) stage (P=0.006). The CIBERSORT method was applied to quantify the relative levels of different immune cell types. It was found that the ratio of eosinophils, mast cells (MCs) resting and CD4 T cells memory activated in the low‑risk group was higher than that in the high‑risk group, and the difference was statistically significant (P=0.003, P=0.014 and P=0.018, respectively). Inconsistently, the ratio of resting natural killer (NK) cells and activated plasma cells in the low‑risk group was significantly lower than that in the high‑risk group (P=0.05 and P=0.009, respectively). Kaplan‑Meier survival results showed that patients of the high‑risk group had significantly shorter overall survival (OS) than those of the low‑risk group in the training set (P<0.001). Furthermore, Kaplan‑Meier survival showed that patients of the high‑risk group had significantly shorter OS than those of the low‑risk group (P=0.0025 and P=0.0157, respectively) in the validation set [GSE31210 and TCGA (The Cancer Genome Atlas)]. The 10‑gene signature was found to be an independent risk factor for prognosis in univariate and multivariate Cox proportional hazard regression analyses (P<0.001). In addition, it was found that the risk model constructed by the 10‑gene signature was related to the clinical related factors in logistic regression analysis. The genetic signature closely related to the immune microenvironment was found to be able to predict differences in the proportion of immune cells (eosinophils, resting MCs, memory activated CD4 T cells, resting NK cells and plasma cells) in the risk model. Our findings suggest that the genetic signature closely related to TIME could predict the prognosis of NSCLC patients, and provide some reference for immunotherapy.

/pdf/a-signature-of-tumor-immune-microenvironment-genes-3wzge1rori.pdf

Chenyue Zhang

Papers

Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1α via the PI3K/AKT/mTOR pathway

Differences in Stage of Cancer at Diagnosis, Treatment, and Survival by Race and Ethnicity Among Leading Cancer Types.

Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression.

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer.