Bioelectric Control of Metastasis in Solid Tumors.

IntroductionCancer is an important public health concern with heavy disease burden in China. In 2017, cancer is the leading cause of death, with around 2.60 million deaths, which accounts for 26.07% of all deaths. This study aims to present cancer mortality in China in 2018 to provide evidence for cancer control and prevention. MethodsMortality data from China Cause of Death Reporting System (CDRS) and population data from National Bureau of Statistics are used for cancer mortality estimation. A descriptive analysis was conducted to demonstrate the results. ResultsA total of 2,557,297 cancer deaths were estimated in China in 2018 with a mortality rate and age-standardized mortality rate of 183.89 and 145.60 per 100,000, respectively. Lung, liver, and stomach cancer were the three leading causes of cancer death and accounted for around 56.75% of all cancer deaths. The age-standardized mortality rate was higher in men (194.37 per 100,000) than in women (99.47 per 100,000), in urban areas (148.25 per 100,000) than in rural areas (144.62 per 100,000), and in eastern regions (150.57 per 100,000) than in central (142.09 per 100,000)/western regions (141.54 per 100,000). The age-specific mortality rate remains low for the population younger than 44 years old and reaches its peak after 80 years old. Leukemia is the leading cause of cancer death among those aged 0–14 years in both sexes, while breast cancer is the leading cause of cancer death in women aged 15–44 years. Conclusions and Implications for Public Health PracticeThe cancer mortality patterns show substantial disparities among sexes, age groups, areas, and regions. Healthy lifestyle promotion, active vaccination uptake, and environmental governance are essential to eliminate cancer-related risk factors in the overall population. Tailored strategies for the early screening and diagnosis, therapeutic management, and palliative care should be a top priority for enforcement among target populations and regions.

BACKGROUND: Colorectal cancer is a common cause of death throughout the world. Approximately 145,290 new cases of large bowel cancer are diagnosed each year in the United States, of which 104,950 are colon and the remainder rectal cancers. In 2005, more than 56,000 Americans will die of CRC, accounting for approximately 10 percent of all cancer deaths. In the United States, CRC ranks second to lung cancer as a cause of cancer death, and it is third both in frequency and cause of cancer death, in men and women separately. In 2004 in Europe, there were an estimated 2 886 800 incident cases of cancer diagnosed and 1 711 000 cancer deaths. The most common incident form of cancer was lung cancer (13.3 % of all incident cases), followed by colorectal cancer (13.2 %) and breast cancer (13 %). Lung cancer was also the most common cause of cancer death (341 800 deaths), followed by colorectal (203 700), stomach (137 900) and breast (129 900). According to the ASO-ASSO (Austrian Society of Surgical Oncology) in Austria CRC is the second most common cancer and the incidence rate is increasing. As in many types of cancer, the lymphatic system is the primary pathway of metastasis, representing the first step of generalisation. However, lymphangiogenesis and the mechanism of lymphatic metastasis in colorectal cancer remain unclear. Aim of this study was to investigate the prognostic role of lymphangiogenesis (LMVD), lymphovascular invasion (LVI) and the lymphangiogenic growth factor VEGF-C in a cohort of colorectal cancers. METHODS: Forty-seven cases of colorectal cancer were investigated. VEGF-C-expression, LMVD, LVI and lymphatic vessel size (LVS) were evaluated semiquantitatively by immunohistochemistry. RESULTS: A significant association was seen between LMVD and LVI (p ≤ 0.005, Mann-Whitney test). LVI correlated significantly with the lymph-node status (p = 0.04, Spearman's coefficient of correlation) and LVS (p = 0.018, Mann-Whitney test). In a mean observation time of 145 months univariate survival analysis showed a significant difference in disease-free survival (DFS) and a clear trend in overall survival (OS) between patients with and without LVI (p = 0.0148 and p = 0.14, respectively, log-rank test). Further VEGF-C-expression in tumor-cells had a significant influence on the OS in univariate survival analysis (p = 0.0391, log-rank test). CONCLUSIONS: These data provide further evidence for the important role of lymphangiogenesis and lymphovascular invasion in the prognosis of colorectal cancer implying new potential anti-tumor targets.

Evolución de la mortalidad por cáncer en Cataluña (1975–1998)

To estimate the impact of smoking-attributable cancer mortality on trends in cancer mortality in New South Wales (NSW), Australia, between 1972 and 2008. The study is a retrospective analysis of cancer mortality in NSW using NSW Central Cancer Registry data. Smoking-attributable cancer deaths were estimated using the smoking impact ratio method, which provides an indirect estimate of exposure to tobacco in the NSW population using lung cancer mortality. Trends in age-standardised cancer mortality rates by cancer type and the number of years of life lost due to smoking-attributable cancer deaths were estimated. In NSW, the cancer mortality rate decreased in males by 26% and females by 19% between 1989 and 2008. Nearly half (44%) of the decrease for males was a result of the decline in smoking-attributable cancer deaths. Despite a decline in the female all-cancer mortality rate, the smoking-attributable cancer mortality rate increased from 20.3 per 100 000 to 26.8 per 100 000 between 1989 and 2008. Smoking-attributable cancer deaths in women increased from around 150 per year in the early 1970s to 1186 in 2008; for men, the number remained stable at just over 2000 deaths per year since the 1980s. Although the lung cancer mortality rate declined in men, lung cancer remains the largest cause of cancer death. Lung cancer has overtaken breast cancer to be the largest cause of cancer death among women, with 17.1% (n = 998) of cancer deaths due to lung cancer in 2008. Despite declining all-cancer mortality in NSW, around 3330 cancer deaths in 2008 were due to the accumulated hazard of smoking in current and ex-smokers. This highlights the importance of tobacco control as part of a comprehensive cancer control plan.

Ovarian cancer is the fourth most frequent cause of cancer death in women and the leading cause of gynecological cancer deaths. More women die of ovarian cancer than from cervical and endometrial carcinoma combined. Roughly 20,000 new ovarian cancer cases are diagnosed every year in the United States and 12,000 women will die. Approximately 1 woman in 70 will develop the disease and about 1% of all female deaths are due to ovarian cancer. A steady increase in age-adjusted ovarian cancer death rates has been observed over the last 4 decades.

Pancreatic cancer is an aggressive and often fatal malignancy with an overall mortality to incidence ratio of 0.98. In 2012, 338,000 new cases were diagnosed worldwide and 330,000 deaths were recorded [1]. In the USA, pancreatic cancer is currently the fourth leading cause of cancer death, but it is projected to become the second leading cause before 2020 [2]. The 5-year survival rate (<5%) is lower than that of all other major cancers. Standard treatment is cytotoxic chemotherapy, which can be effective, but disease progression generally ensues within 6–12 months. The only potentially curative therapy is surgery, but less than 20% of patients are candidates for surgery and among those who undergo surgery, the 5-year survival rate is 15%, highlighting the fact that the vast majority of patients have occult metastatic disease at the time of presentation. Population-based screening programs for pancreatic cancer are not feasible owing to the very low absolute individual risk, as well as the lack of non invasive and low-cost screening tools. Hence, identifying biomarkers of risk that could be useful in high-risk individuals is essential. o besity, diabetes & pancreatic cancer There is compelling data linking obesity and diabetes with pancreatic cancer risk and survival [3,4]. Obese individuals with a BMI of ≥35.0 have a significant increased risk of pancreatic cancer compared with individuals with normal weight (BMI: 18.5–24.9). Furthermore, every 5 kg/m 2 increase in BMI is associated with a 12% increased risk of pancreatic cancer [5]. The association of obesity with pancreatic cancer risk is not limited to obesity during adult life, as obesity during adolescence and early adulthood also confer increased risk. Likewise, the association of diabetes with pancreatic cancer risk is established [6]. In a meta-analysis of cohort studies, diabetes was associated with a 1.94-fold increased risk of pancreatic cancer [6]. A challenge in epidemiological studies investigating the association of diabetes with pancreatic cancer risk is the concept of reverse causality. Pancreatic cancer causes diabetes, and an estimated 34% of pancreatic cancer patients may have pancreatic cancer-induced diabetes [7], hence, onset and duration of diabetes are

Background Ovarian cancer (OC) is the eighth most common cause of cancer death and the second cause of gynecologic cancer death in women around the world. Ferroptosis, an iron-dependent regulated cell death, plays a vital role in the development of many cancers. Applying expression of ferroptosis-related gene to forecast the cancer progression is helpful for cancer treatment. However, the relationship between ferroptosis-related genes and OC patient prognosis is still vastly unknown, making it still a challenge for developing ferroptosis therapy for OC. Methods The Cancer Genome Atlas (TCGA) data of OC were obtained and the datasets were randomly divided into training and test datasets. A novel ferroptosis-related gene signature associated with overall survival (OS) was constructed according to the training cohort. The test dataset and ICGC dataset were used to validate this signature. Results We constructed a model containing nine ferroptosis-related genes, namely, LPCAT3, ACSL3, CRYAB, PTGS2, ALOX12, HSBP1, SLC1A5, SLC7A11, and ZEB1, and predicted the OS of OC in TCGA. At a suitable cutoff, patients were divided into low risk and high risk groups. The OS curves of the two groups of patients had significant differences, and the time-dependent receiver operating characteristics (ROCs) were as high as 0.664, respectively. Then, the test dataset and the ICGC dataset were used to evaluate our model, and the ROCs of test dataset were 0.667 and 0.777, respectively. In addition, functional analysis and correlation analysis showed that immune-related pathways were significantly enriched. Meanwhile, we also integrated with other clinical factors and we found the synthesized clinical factors and ferroptosis-related gene signature improved prognostic accuracy relative to the ferroptosis-related gene signature alone. Conclusion The ferroptosis-related gene signature could predict the OS of OC patients and improve therapeutic decision-making.

Lung cancer is the leading cause of cancer deaths for both men and women in the United States. Lung cancer exceeded breast cancer as the primary cause of female cancer deaths in 1987 and now kills more women than the next two most common cancers in females (breast and colorectal) combined. The rate of lung cancer diagnoses for men has declined in the last 30 years; however, lung cancer incidence has risen for women. Whether or not women have an increased risk of lung cancer remains controversial. There is, however, no debate to the fact that the biology of lung cancer differs between the sexes. Here we review the explanations for the observed sex differences in lung cancer presentation, including disparities in clinical characteristics, genetic factors and hormonal influences, as well as variations in incidence rates, outcomes, and therapeutic response. Finally, the current status and future implications for pharmacological blockade of the estrogen pathway for lung cancer treatment are discussed.

Since the cancer has been the leading cause of deaths in Korea, estimation of the cancer deaths for the upcoming years in the population using the vital statistics is considered to be necessary. The aim of this study was to estimate the number and trends of cancer deaths in Korea. The expected numbers of cancer deaths were calculated by a time series model fitting the actual numbers of cancer deaths for each of the years 1983 through 2000 reported by Korea National Statistical Office. The options selected for the time series model included a quadratic time trend, which incorporated long-term information into the model and an autoregressive component which incorporated information about short-term fluctuations. The forecasting numbers of cancer deaths and their 95% confidence intervals were estimated for both genders and primary sites. The forecasting number of deaths from all cancers is increasing so that the cumulative number of expected cancer deaths between 2001 and 2005 would be about 309 thousand persons. Cancers of the lung, stomach, liver, and colorectum continue to be the most common causes of cancer deaths. While the numbers of expected cancer deaths in the stomach and liver show a decreasing trend, the cancer in the lung, colorectum, pancreas, breast, and oral cavity have an increasing trend. These observations indicate that cancer deaths in the near future would be increasing through the early 2000s, and there should be some urgent government's policy on the cancer management.

Introduction: Cancer is the leading cause of death in economically developed countries and second leading cause of death in developing countries. Despite the high cancer mortality rates in developing countries the contribution of cancer to death in surgicalpractice has not been determined in our institution. An analysis of cancer deaths in the department of surgery at the Korle Bu Teaching Hospital is presented.Methods: All cases of cancer deaths from 1st January 1998 to 31st December 2013 were retrieved and retrospectively reviewed. The sex, age, primary tumour site, period of admission prior to death, cause of death and post-mortem findings formed the primary data for the analysis.Results: There were 113,960 admissions in the surgical department of KBTH over the fifteen year period, with 4,979 overall deaths, of which 1,637 were cancer mortalities, representing 32.85% of the total mortality and a cancer mortality rate of 1.44%. The commonest cancer deaths were from breast (14.48%), prostate (12.52%), colorectal (9.65%), gastric (8.74%) and pancreas (8.67%). Brain tumoursand Wilm’s tumours accounted for 37% and 21% respectively of cancer mortalities in the paediatric age group. Cancer mortalities in the adolescent age group showed many cases of nasopharyngeal cancers (15.85%). Lung cancers accounted for only 1.16% of cancer mortalities in the institution.Conclusion: Cancer accounted for a third of the deaths in the surgical department of KBTH with breast and prostate cancers being the leading overall causes of cancer deaths. Deaths due to lung cancer were low contrasting with the world trend.

Lung cancer is now the leading cause of cancer death in both men and women in China, accounting for 21.7% of estimated cancer deaths in 2015 (1). Lung cancer is also the leading cause of cancer death in men and the second leading cause of cancer death in women worldwide (2).

Background: Lung cancer is the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide. Rates are highest in countries where smoking uptake began earliest, such as those in North America and Europe. Although rates are now decreasing in most of these countries, especially in men, they are increasing in countries where smoking uptake occurred later. Variation between countries may reflect different prevalence of risk factors. Lung cancer is the leading cause of cancer death among both men and women in the United States. In the United States, smoking rates among women peaked after those among men. The main objective is to estimate age-standardized mortality rates by U.S. county from tracheal, bronchus, and lung cancer. Methods: The finding of the Global Burden of Disease (GBD) 2015 methodology with death records from the National Center for Health Statistics (NCHS) and population counts from the Census Bureau, the NCHS, and the Human Mortality Database from 1980 to 2014 were used. Results: A total of 5,656,423 deaths from tracheal, bronchus, and lung (TBL) cancer were recorded. There were large differences in the mortality rate among counties throughout this period. TBL cancer mortality declined by 21.0% (95% UI, 17.9%-24.0%) between 1980 and 2014, from 68.6 (95% UI, 66.8-70.3) deaths per 100,000 population to 54.2 (95% UI, 52.7-55.6). The West and Northeast experienced declines in the mortality rate, as did Florida, while increases were observed in the South, Appalachian region. The largest increase from 1980 to 2014 was observed in Owsley County, Kentucky (99.7%; 95% UI, 73.7%-130.8%), while the greatest decline was observed in Aleutians East Borough and Aleutians West Census Area, Alaska (63.6%; 95% UI, 50.3%-73.5%). High mortality rates in 2014 were clustered in West Virginia. Because national rates peaked in 1988, women in 2,215 counties experienced a statistically significant increase in the mortality rate, while this was true for men in only 11 counties. The highest national mortality rate for men was present in 1980, while the peak in mortality rate for women was in 2001. The largest percentage increase (168.3%; 95% UI, 136.4%207.8) from 1980 to the peak in 2001 for women was observed in Marlboro County, South Carolina (mortality rate of 67.1 deaths per 100 000). Mortality rates varied from 10.6 (95% UI, 8.6-12.8) in Summit County, Colorado, to 334.9 (95% UI, 300.5-375.2) in Union County, Florida, for males and 10.9 (95% UI, 8.3-13.8) in Summit County, Colorado, to 121 (95% UI, 101.6-142.0) in Owsley County, Kentucky, for females. Low rates were observed along the US border with Mexico and in Utah, Colorado, and parts of Arizona, New Mexico, and Idaho. Conclusion: From 1980 to 2014 there has been a steady decline in the cancer death rate as a result of fewer Americans smoking and advances in cancer prevention, early detection, and treatment. Local efforts to reduce smoking in poor and rural areas are needed to reduce the burden of smoking-related cancer and other diseases. Note: This abstract was not presented at the conference. Citation Format: Miloud Taki Eddine Aichour, Zoubida Zaidi. Trends and patterns of disparities in tracheal, bronchus, and lung cancer mortality among U.S. counties, 1980-2014 [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A10.

Lung cancer and liver cancer are the leading and third causes of cancer death, respectively. Both lung and liver cancer are with clear major risk factors. A thorough understanding of their burdens in the context of globalization, especially the convergences and variations among WHO regions, is useful in precision cancer prevention worldwide and understanding the changing epidemiological trends with the expanding globalization. The Global Burden of Disease (GBD) and WHO Global Health Observatory (GHO) database were analyzed to evaluate the burden metrics and risk factors of trachea, bronchus, and lung (TBL) cancer and liver cancer. Western Pacific Region (WPR) had the highest age-standardized incidence rate (ASIR) for both liver cancer (11.02 [9.62–12.61] per 100,000 population) and TBL cancer (38.82 [33.63–44.04] per 100,000 population) in 2019. Disability-adjusted life years (DALYs) for liver and TBL cancer elevated with the increasing sociodemographic index (SDI) level, except for liver cancer in WPR and TBL cancer in European Region (EUR). Region of the Americas (AMR) showed the biggest upward trends of liver cancer age-standardized rates (ASRs), as well as the biggest downward trends of TBL cancer ASRs, followed by Eastern Mediterranean Region (EMR). Alcohol use and smoking were the leading cause of liver and TBL cancer death in most WHO regions. Variances of ASRs for liver and TBL cancer among WHO memberships have been decreasing during the past decade. The homogenization and convergence of cancer burdens were also demonstrated in different agegroups and sexes and in the evolution of associated risk factors and etiology. In conclusion, our study reflects the variations and convergences in the liver and lung cancer burdens among the WHO regions with the developing globalization, which suggests that we need to be acutely aware of the global homogeneity of the disease burden that accompanies increasing globalization, including the global convergences in various populations, risk factors, and burden metrics.Graphical

BackgroundMetastasis is the number one cause of cancer deaths. Expression microarrays have been widely used to study metastasis in various types of cancer. We hypothesize that a meta-analysis of publicly available gene expression datasets in various tumor types can identify a signature of metastasis that is common to multiple tumor types. This common signature of metastasis may help us to understand the shared steps in the metastatic process and identify useful biomarkers that could predict metastatic risk.MethodsWe identified 18 publicly available gene expression datasets in the Oncomine database comparing distant metastases to primary tumors in various solid tumors which met our eligibility criteria. We performed a meta-analysis using a modified permutation counting method in order to obtain a common gene signature of metastasis. We then validated this signature in independent datasets using gene set expression comparison analysis with the LS-statistic.ResultsA common metastatic signature of 79 genes was identified in the metastatic lesions compared with primaries with a False Discovery Proportion of less than 0.1. Interestingly, all the genes in the signature, except one, were significantly down-regulated, suggesting that overcoming metastatic suppression may be a key feature common to all metastatic tumors. Pathway analysis of the significant genes showed that the genes were involved in known metastasis-associated pathways, such as integrin signaling, calcium signaling, and VEGF signaling. To validate the signature, we used an additional six expression datasets that were not used in the discovery study. Our results showed that the signature was significantly enriched in four validation sets with p-values less than 0.05.ConclusionsWe have modified a previously published meta-analysis method and identified a common metastatic signature by comparing primary tumors versus metastases in various tumor types. This approach, as well as the gene signature identified, provides important insights to the common metastatic process and a foundation for future discoveries that could have broad application, such as drug discovery, metastasis prediction, and mechanistic studies.

The ion channels are distributed in all cells and promote the rapid influx of ions that underlie the formation of cellular bioelectrical signals. Bioelectrical signals coupled with other regulator mechanisms provide fundamental physiological cellular processes, such as cellular differentiation, proliferation, and apoptosis, which are strongly associated with the manifestation of cancer hallmarks. Alterations in the bioelectrical signaling mechanism underlie the unusual bioelectrical features of cancer cells. Investigating the role of bioelectrical signals in tumor growth provides fundamental insights into cancer diagnosis and tumor-targeted treatment. Hence, this field of research is becoming one of the frontrunners of cancer medicine, and advances in biophysical tools are enabling progress in understanding this biological phenomenon. Recent studies have revealed that bioelectrical signals represent a promising target in cancer therapy. It is becoming increasingly convincing that cancer conditions can be reversed to normal by regulating the bioelectrical signaling mechanism of cells. Herein, we provide a brief review of the role of bioelectrical signals in cancer pathophysiology and provide data on the manipulation of this signaling mechanism as a novel approach to preventing malignant growth.