Proportion Of Cancer-related Deaths Research Articles

Pancreas Β-Cells in Type 1 and Type 2 Diabetes: Cell Death, Oxidative Stress and Immune Regulation. Recently Appearing Changes in Diabetes Consequences.

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements. It has been suggested that autophagy promotes β-cell survival by delaying apoptosis and providing adaptive responses to mitigate the detrimental effects of ER stress and DNA damage, which is directly related to oxidative stress. As people with diabetes are now living longer, they are more susceptible to a different set of complications. There has been a diversification in causes of death, whereby a larger proportion of deaths among individuals with diabetes is attributable to nonvascular conditions; on the other hand, the proportion of cancer-related deaths has remained stable or even increased in some countries. Due to the increasing cases of both T1D and T2D, these diseases become even more socially significant. Hence, we believe that search for any opportunities for control of this disease is an overwhelmingly important target for the modern science. We focus on two differences that are characteristic of the development of diabetes's last periods. One of them shows that all-cause death rates have declined in several diabetes populations, driven in part by large declines in vascular disease mortality but large increases in oncological diseases. Another hypothesis is that some T2D medications could be repurposed to control glycemia in patients with T1D.

Personalized treatment of cholangiocellular carcinoma (CCA)

Cholangiocellular carcinoma (CCA) is one of the primary liver tumors and overall represents a rare malignancy; however, in recent years the incidence, particularly of intrahepatic CCA (iCCA) has increased worldwide. Due to the high mortality, CCAs cause asignificant proportion of cancer-related deaths also in Germany. Because the diagnosis is often made in advanced stages of the disease, in many cases asurgical approach with curative intention is not possible. For locally advanced or metastatic CCA the combination of gemcitabine and cisplatin currently remains the only approved systemic treatment. As the average survival time is only approximately 12months even under first-line treatment with gemcitabine/cisplatin, research is focused on developing new molecularly targeted and immunological treatment options. Various studies are currently being carried out to investigate approval options for targeted treatment, which could be considered for genetically altered tumors, e.g. in fibroblast growth factor receptor (FGFR) fusion and isocitrate dehydrogenase (IDH) mutations. Additionally, initial clinical data on immune checkpoint inhibitors are available for CCA. Due to the complex selection and partially limited applicability of current treatment options in patients with CCA, an early collaboration with a gastroenterology and oncology center with the possibility of supervision by a tumor board consisting of gastroenterological oncologists, surgeons, radiologists and radio-oncologists or in advanced stages by a molecular tumor board is essential.

Mortality profile in pediatric malignancies: a 11 year retrospective study

Background: Malignancy is one of the leading causes of childhood deaths in developed nations while diarrheal and respiratory infections continue to compete in many developing nations. Since the state of Goa, has health statistics comparable to the western world, an attempt has been made to look at the childhood cancer mortality in proportion to overall deaths in the only tertiary care hospital in the stateMethods: In the absence of a population registry, information was obtained from the hospital mortality statistics during the period from January 2007 to December 2017.Results: A total of 118 cancer deaths were seen over a period of 11 years with a male/female ratio of 1.34:1. The proportion of cancer deaths to total deaths due to any cause, per year was 11.9%. Most of the deaths were noted in the 1-10 years age group (53.4%) with maximum deaths seen in hematological malignancies (50.8%).Though sepsis was the immediate cause of death in 42(35.6%), a significant drop was noted in last 5 years wherein it was observed to fall from 22.8% in the initial 6 years to 12.7% in the latter 5 year period.Conclusions: Proportion of cancer related deaths were seen to reduce over the study period with a significant drop, in sepsis, as the major cause. Simple measures to control sepsis may help to reduce cancer mortality.

Iron levels, genes involved in iron metabolism and antioxidative processes and lung cancer incidence.

BackgroundLung cancer is the most common adult malignancy accounting for the largest proportion of cancer related deaths. Iron (Fe) is an essential trace element and is a component of several major metabolic pathways playing an important role in many physiological processes. In this study we evaluated the association between Fe concentration in serum, iron metabolism parameters and genetic variaton in 7 genes involved in iron metabolism and anti-oxidative processes with the incidence of lung cancer in Poland.Materials and methodsThe study included 200 lung cancer patients and 200 matched healthy control subjects. We analyzed serum iron concentration and iron metabolism parameters (TIBC, UIBC, serum ferritin and transferrin saturation), and genotyped seven variants in seven genes: HFE, TFR1, HAMP, TF, SOD2, CAT and GPX1.ResultsLung cancer patients compared to their matched controls had significantly higher mean serum iron level (p = 0.01), ferritin level (p = 0.007) and TIBC (p = 0.006). Analysis revealed that higher concentration of iron and ferritin (IVth quartile) compared to the lower concentration (Ist quartile) was associated with over 2-fold increased lung cancer incidence. We also found that higher transferrin saturation (p = 0.01) and lower TIBC (p<0.01) are associated with better survival of lung cancer patients. The analysis of polymorphisms in iron related genes did not reveal a significant difference between lung cancer patients and controls. However, rs10421768 in HAMP showed a borderline statistically significant correlation with lung cancer risk (OR = 2.83, p = 0.05).ConclusionsThe results of this case control study indicate that higher body iron represented by higher Fe and ferritin levels may be associated with lung cancer incidence. Rs10421768 in HAMP may be associated with about 3-times higher lung cancer risk. Higher Fe body content may be associated with better survival of lung cancer patients.

Abstract P6-01-18: Early detection of development of a pre-metastatic niche in lungs in response to primary breast tumor using Raman spectroscopy

Abstract Background: An alarmingly large proportion of cancer-related deaths result from metastatic cancers. Development of quick, reliable and non-invasive or minimally invasive approaches to objectively assess the secondary tissues (potentially in vivo) will be instrumental in substantially reducing the cancer burden due to metastasis, which accounts for majority of cancer related mortality. In our study we report the utilization of Raman spectroscopy and chemometric techniques in identifying formation of pre-metastatic niche in lungs prior to observing morphological changes. Methods: Six-week-old female athymic nu/nu mice (NCI, MD) were implanted with 2x106 cells of human breast cancer cell lines - MDA-MB-231 (n=3), and MCF-7 (n=3) in their fourth right mammary fat pad orthotopically. And control mice (n=3) without tumor cell implantation were also employed. The primary tumor size was monitored and the mice were sacrificed within 8-12 weeks of cell implantation when the primary tumors volume grew to 500-600 mm3. Control mice were also sacrificed in this timeframe. The freshly excised lungs of the mice were cleaned in PBS and utilized for obtaining Raman spectra (830 nm, thermoelectrically cooled CCD). Each tissue was collected from multiple points. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) were employed as discriminating algorithm. Following spectral acquisition, the tissues were fixed in 10% formalin, embedded in paraffin, and then HE staining, and Masson's trichrome staining for collagen. Collagen quantification of Masson's trichrome stained slides was achieved using MATLAB (Mathworks, MA). The Institutional Animal Care and Use Committee at Johns Hopkins University School of Medicine approved the protocol of the study. Results: 900 Raman spectra each acquired from the lungs of the control mice and mice bearing MCF-7 and MDA-MB-231 tumor xenografts were assigned class labels - 'Control', 'MCL' and 'MDL' respectively for further analysis. Select principal components from those obtained by subjecting all the chosen 900 spectra to PCA clearly evident that the differences in the Raman spectra belonging to tissues being primed by derivatives of different primary cells are quite pronounced. The average correct rates of PLS-DA prediction of 90.1%, 97.7% and 78.4% were obtained for the spectra belonging to the classes - Control, MCL and MDL respectively. The HE images are negative for any signs of cancerous lesions. Masson's trichrome staining results show that the metastatic potential of the cell lines responsible for the primary tumor is positively correlated with the collagen density in the pre-metastatic niche, the MDL shows the highest collagen density (P&amp;lt;0.001). These differences clearly indicate the remodeling of extracellular matrix anticipating incoming tumor cells in response to primary tumor derived factors occurs very early in the metastatic cascade. Conclusion: The current study introduces Raman spectroscopy in conjunction with chemometric techniques as are liable and minimally invasive tool for diagnosis of metastatic cancers significantly early in the metastatic cascade, and also opens a new route for early targeting of cancer metastasis and its associated burden. Citation Format: Zheng C, Rizwan A, Paidi SK, Yu Z, Barman I, Glunde K. Early detection of development of a pre-metastatic niche in lungs in response to primary breast tumor using Raman spectroscopy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-18.

Unusual Aggressive Breast Cancer: Metastatic Malignant Phyllodes Tumor

For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

Race Disparities between Black and White Women in the Incidence, Treatment, and Prognosis of Endometrial Cancer

Uterine cancer is the most common gynecologic malignancy in the United States, with an estimated 40,100 new cases and 7,470 deaths occurring in 2008. Although the incidence of endometrial cancer is lower among black women compared with white women, the proportion of cancer-related deaths among blacks is higher and has continued to rise over the past two decades. The authors conducted a survey of recent literature published in the English language and have used these articles as the basis for this review. The etiology for the racial disparity among black women with endometrial cancer is multifactorial and may be the result of barriers that impede access to care, an increased incidence of comorbidities among black women, inequalities in surgical care, adjuvant chemotherapy and radiation treatment, and underlying biological differences associated with more aggressive tumors that often develop in black women. Black women with endometrial cancer have a poorer prognosis compared with white women. Factors that contribute to this racial disparity include later diagnosis, treatment disparities, comorbid conditions, and genetic differences in tumors. An improved understanding of the causative factors associated with racial disparities in endometrial cancer outcome is needed to facilitate efforts aimed at correcting this important health care problem and providing individualized care to those at highest risk for poor outcome.