In addition to the genetic analyses described above, which used an SNP array and Comprehensive Cancer Panel, we performed a series of western blot analyses to check the levels of the major growth signaling and cell cycle regulatory proteins that have previously been implicated in pancreatic cancer [14–17]. Accordingly, we found heterogeneous expression levels of these proteins (Figure 5). In particular, we observed the frequent loss of TP53 expression (by approximately 50%), as well as the minimal expression of P16. In contrast, we detected various levels of p-BRAF and p-MEK, which are major downstream effectors of K-Ras . Interestingly, some of the PDXs (#4, 9, and 15) showed discordant p-BRAF and p-MEK levels, suggesting that some alternative pathway activates p-MEK in these tumors. We detected a relatively consistent level of p-AKT and SMAD4, whereas the levels of p-ERK and MTAP varied greatly. Therefore, our protein analysis revealed that the PDXs have a heterologous molecular nature that resembles the known heterologous character of primary tumors , supporting the strategy of using PDX as a preclinical model in pancreatic cancer.
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characterizing TAAs in DFTD compared to similar strategies in humans (where the heterogeneity of tumour cells is high, even among patients affected by the same type of cancer) is the clonal nature of the tumours and the stability of the DFTD genome (Murchison et al., in press). This means that tumour antigens are more likely to be conserved and that the immune response will have a constant antigenic target, aspects that are essential for the development of a vaccination approach (Woods et al., 2007). In human cancer, humoral responses develop as part of the immune response to changes in protein structure and/or expression (Tabernero et al., 2010). These proteins are likely to have a role in tumour growth by regulating processes such as cell proliferation, angiogenesis and tumour invasion. Therefore, the identification of these antigens in devil facial tumour cells is also relevant for the understanding of underlying carcinogenesis processes. Examples of the DFTD TAAs identified include the 14-3-3 protein and HSP-90, which contribute to regulating the cell cycle, survival and migration; aconitate hydratase protein which plays an important role in cellular bioenergy production; and cathepsin B that has been involved in cancer progression and metastases. The fact that these processes have been considered hallmarks of cancer (Hanahan and Weinberg, 2011), indicates that these mechanisms may play an important role in the development of devil facial tumours.
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(Supplementary Figure 1e). Duplicate WA values per cell line were then averaged and used for downstream analysis. The distributions of WA scores were comparable to the WA distributions in other normal and cancer cell Repli-Seq datasets (Supplementary Figure 1f). Early- and late-replicating regions were deﬁned as those regions in the top and bottom 10% of WA scores in both cell lines. This deﬁnition gives upper and lower limits of 75 and 20 respectively for PrEC and LNCaP (i.e. early regions have WA > 75 and late regions WA < 20). WA thresholds for a change in timing were deﬁned by the following process: differences in WA between replicates of the same cell line are representative of random noise and therefore can be used as an empirical null distribution for the hypothesis test that the WA difference between LNCaP and PrEC is equal to zero. The maximum observed difference, in our data, between replicates is |ΔWA| = 23 (Supplementary Figure 1h). To be conservative, we chose a cut-off of | Δ WA| > 25 as a value that occurs infrequently (or never) by chance under the null. Differences in WA that are larger than ±25 ΔWA are therefore considered to show a robust change in replication timing. To identify domains of loci with changed replication timing, we merged all loci within 50 kb that had | Δ WA| > 25. On average, altered replication timing domains were ~295 kb wide. For MCF7, the top 10% of early- and late-replicating loci gives upper and lower WA limits of 73 and 17.
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In one form of CAR-T-cell immunotherapy called TIL, T-cells that are naturally able to recognize and attack cancer cells but are limited in number, are collected from the surfaces of the solid tumor tissues. They are then grown ex-vivo, outside the body of the patient in huge numbers and then given back to the patient so that they attack and kill the cancerous cells. This method has been successful at least in one case of cholangiocarcinoma  at NIH. Cancer vaccines may also be used to trigger the action of T-cells that remain inactive against the cancer cells. Antibodies may be used to detect and capture either the cancer cells or the immune cells. Under ideal circumstances, tumor cells will have peptide or protein residues hanging off them that can act as antigens which can be recognized by T-cells as foreign bodies and attacked through the antigenic response system. Tumors develop many mutations. Some of those mutations lead to production of entities (antigens) that extend outside their cells, in the form of a peptide. For example, the EGFRvIII mutation is one such mutation that extends a peptide piece outside the cell which provides an opportunity for raising antibodies against them. Such antibodies can then be used as drugs to help kill the tumor cells. Once T-cells recognize the cancer cells with antigens, they proceed to capture, lyse and kill those cancer cells and thus destroy the tumor. Of course, there are several types of T-cells each of which have different defensive duties which they perform by utilizing different mechanisms.
Cancer is the second most common cause of death in the developed world and a similar trend has emerged in the developing countries too (Goyal PK (2012). The study analyzes the understanding of the extent of social support among cancer patients in institutional settings. The study was conducted among the cancer patients in six palliative care clinics in Wayanad district, Kerala. It tries to pursue the two important research questions. (1) To identify the social support persons or groups who extend social support to the cancer patients. (2) Identify the various types of cancer occurring among the cancer patients in institutional settings. A descriptive research design was followed for conducting the study. The population which is included in this study was about 46 respondents who were under treatment in the six palliative care clinics in the district. The investigator conducted intuitional visits for data collection; informal consent was obtained from each respondent, followed by the distribution of socio economic data sheet and the Social Support Appraisal Questionnaire (Alan Vaux, 1987). Following the data collection, a data analysis was carried out. The findings of the study clearly revealed that most of the patients came out from the nuclear family and belonged to poor socio- economic status. The study pointed out the significance of psycho education among the family members and the society. This attempt will be helpful to the patient to ensure various kinds of social support towards the recovery from the disease.
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It is now almost half a century since the overthrow of Ehr- lich's doctrine of "horror autotoxicus" and the general acceptance of the contrary idea that animals can indeed be immunized against the growth of a transplanted syn- geneic cancer. Why then is it that, despite nearly 50 years of intense investigation, attempts to use the immune reac- tion as a tool against cancer have, with the exception of bladder cancer, met with only moderate success? What is the realistic prospect that the next 50 years will see an improvement in this dismal state of affairs? Many investi- gators, myself included, have a large vested interest in the field of cancer immunology and will be reluctant to enter- tain any discouraging viewpoint, but the actual facts are, I believe, discouraging.
In hepatic neoplasm, Osteopontin (OPN) , Alfa-Feto Protein (AFP) and heterogeneous nuclear ribonucleoprotein A1 are involved in tumour growth and metastasis and could be used as target site for cancer treatment. Aptamers specific to these protein have shown drastic reduction in tumour formation in liver cell in in vitro conditions [66,67]. Xu and group in 2015  selected seven aptamers through cell-SELEX method that are specific for liver cancer cell (HepG2 cell line) but not to normal cells. Further they also concluded that these aptamers also bind with lung cancer, ovarian cancer and luminal A subtype breast cancer cells, showing multi specific nature of these aptamer in recognizing cancer cells and could be used in cancer therapy. P12FR2 RNA aptamer is specific to pancreatic adenocarcinoma up-regulated factor (PAUF), and could be used in treatment of pancreatic cancer. This aptamer binds with PAUF and inhibit metastasis process in cancer . Other aptamers such as NOX-A50 and NOX-f33 (polyethylene glycol-modified Spiegelmers) are specific to A1 High Mobility Group (HMGA1) proteins which are involved in anchorage-independent growth and epithelial-mesenchymal transition in normal cells making them cancerous one . Epidermal growth factor receptor
The set of photographs was selected to include a variety of environmental features, forms, and flora generally representative of the landscape in southern Ontario (e.g., different deciduous and coniferous trees, bodies of water, flowering plants, hills, etc.). Additionally, some photographs depicted settings that reflected obvious human influence and examples of the built environment, including paths, roads, cars, high-rise and low-rise buildings, and people. Overall, there was a high degree of variability among the photographs, which in turn allowed participants to sample highly differentiated content during construct elicitation. However, the photographs still comprised a relatively homogeneous sample, or range of convenience, meaning that none of the elements were so different or unique that they might not be considered examples of natural places. Heterogeneous samples of elements can complicate the construing procedure because they can exist outside of one’s range of convenience for a given context (Fransella et al., 2004), thus, rendering the constructs inappropriate and/or irrelevant. As such, while the photographs displayed varying degrees of natural and built elements, they all displayed content expected to fit within a range of convenience related to nature and natural spaces in Ontario. Further, none of the photographs contained visual information that would have been considered “novel,” instead depicting common representations of parks, trails, open space, urban green space, and natural features of the landscape that are commonly associated with Ontario’s natural environment. In fact, most photographs were captured within 300 km of each individual’s home.
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Recent discredit of “somatic mutation” hypotheses forced the need of new paradigms about the nature of human cancer. The present article is devoted to fur- ther development of one such paradigm: the hypothe- sis of invasive parasitic nature, origin, evolution, pathogenesis and transmission of human cancer. De- velopment was performed by supplementing and supporting the hypothesis by data which could not be applied before. The supplementation included inte- grative reconsidering, and reinterpretation of the make-ups, traits and processes existing not only in human cancer but also in animal cancers. Special attention has been focused on xenogamous intrusion of carcinogenic traits in the genome of a host. It was evidenced that human cancer possesses the same set of traits characteristic of transmissible animal cancer. In contrast to animal cancer formed of solitary cell lineage, human cancer consists of a couple of lineages constructed under different genetic regulations and performed different structural and physiological functions. The diversity of cancer composition re- mains stable over sequential propagation. The sub- sistence of human cancer regularly includes obliga- tory rotation alternation of its successive forms in- cluding genomic, gametic, zygotic, micro-population and tumorous ones. Human cancer possesses its own biological watch and the ability to gobble its victim, transmit via the intrusion of the genome, perform intercommunications within the tumor components and between the dispersed subunits of cancer.
available for collecting data across the whole of the country, data from rural areas may be impacted by limited health facil- ities, number of professionals and data distributions system compared with 3 urban locations in the country – the city of Ulaanbaatar (UB) and the larger provinces of Darkhan-Uul and Orkhon. A strong relationship between breast cancer and age has also been identified among Mongolian women with the highest incidence rate of 28.4/100,000 occurring among the 50–54 years old compared to 3.7 per 100,000 in the 15–39 age group. 2 Although the peak age appears to be
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Review of literature and issues for research: The review of the literature in the relevant field gives a conclusion that illness or diseases of workers not only affect the workers themselves but also the employers an there are certain epidemics as HIV/AIDS have significant impact on world of work. Some authors also linked the mental health, stress and different technologies. Some mentioned that the production cost and efficiency mainly depends on workers health and safe etc. Leser (1947) mentioned that much sickness and fatal disease amongst wage earners is directly or indirectly due to the nature of workers employment. The conditions surrounding the job, air, heat light and physical strain may affect the workers health adversely miners for instance are likely to contract asthma, silicosis and tuber colossi. Hyeshook Park (2002) in his study found that overall mortality rate and accident rate among these enterprises was not better than national average. As for occupational health hazard in these workers number of hazard per work place was smaller but the profession of exposed workers per workplace was higher as compared to the larger companies. Ashish and Papri (2004) in their article mentioned about inter relation between mechanization of process of production, quality of workers and their life, say decent workplace remain a distant reality. Gradual mechanization of the process of production combined with effective managerial strategies have allowed the employers to achieve greater control over the process of production. Apart from the above reviewed studies, still there are numerous studies on OHS of workers in (Abeysekera and Shananavar 1988, Ahasan 2001a, Ahasan 2001, Ahasan and Ertain 2001, Brown and Nguyen- Scatt 1992, Clernstine 2002, Elglstrand 1985, Jahan 1989, Kagi 1998, Leanien 2000, Raihan 1997, Takala 2002, Zohar 1980, Ahasan 2002 and Zaid 2002, Ametepeh, Adei and Arhin 2013, Vinotha P, Surviya R. and Valarmathi 2015). None of them however, adequately addressed what are the socio- economic conditions of the SSI workers? What is the magnitude of common occupational health and safety measures among SSI workers? What are the major occupational health problems that are being faced by the SSI workers in work place ? These aspects though important they are have not been examined comprehensively as yet. It is therefore important to know the above mentioned research questions on OHS of worker in SSIs in India in general and in
Abstract. European grasslands encompass a wide range of habitats that vary greatly in terms of their management, agricultural productivity, socio-economic value and nature conservation status, reflecting local differences in physical environment and economy, the effects of traditional practices and impacts of recent management. Widespread loss of biodiversity, as well as other environmental problems, have resulted from agricultural intensification or abandonment. Policies that have contributed to this have been progressively revised, initially by agri-environment schemes, and subsequently through changes in farm support payments and stricter regulatory frameworks, though many threats remain. We consider the agricultural implications of grassland biodiversity in terms of impacts on herbage production, feed intake and forage quality. Grassland biodiversity is both an externality of particular environments and farming systems and also contributes to objectives of multi-functional land-use systems. In addition to meeting species conservation and habitat protection, grassland biodiversity can contribute to enhanced value of agricultural products of regional, nutritional or gastronomic value, and to non-commodity outputs: agro-tourism, ecosystem functions linked to soil and water quality, and resilience to environmental perturbation. Needs and to conserve and improve the biodiversity potential of agricultural grasslands of typical moderate/high-input management, and for marginal, including communally managed large scale grazing systems, are considered using examples from contrasting areas of Europe. These include reindeer grazing in northern Fennoscandia, winter grazing in the Burren, Ireland, and cereal-fallow sheep grazing system of La Mancha, Spain.
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Over the last few decades, premature mortality from non-communicable diseases (NCDs) before age 70 has dropped in almost all countries . However, additional efforts are needed to achieve a further reduction of 30% by 2030. SDG Goal No. 3 on Good health and wellbe- ing promotes healthy living for all and lists a number of important targets to be achieved. For NCDs it aims to reduce premature mortality by one-third through pre- vention and treatment, and promote mental health. SDG Goal No. 15 on Life on Land proposes we take care of our planet. This includes stopping deforestation, land deg- radation and loss of animal and plant species, i.e. biodi- versity loss. Contact with nature educates the human immune system and endorses tolerance against a vari- ety of exposures being thus an essential determinant of health . All the 17 goals are highly interconnected and in many cases progress in one depends on progress in
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diminished by alcohol consumption which is compatible with the increased breast cancer risk associated with low folate levels occurring only among regular alcohol drinkers. 31 However, with regard to survival from breast cancer, it is less clear how folate and alcohol would interact. Perhaps, alcohol diminishes the amount of folate available, and thus the pro-carcinogenic properties (e.g. increased proliferation) of folate that are proposed to occur later in tumor development are diminished, which is consistent with the timing of alcohol’s effects as suggested to occur later in tumorigenesis. This would be compatible with the finding in our data that alcohol consumption did not lead to tumors with high proliferation, as indicated by the Ki-67 index, however, we were unable to directly test a mechanism involving folate because our study did not collect
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The primary source of these alkaloids are four bryozoan species belonging to the Family Flustridae: Chartella papyracea (Ellis & Solander, 1786), Securiflustra securifrons (Pallas, 1766), Hincksinoflustra denticulata (Busk, 1852) and Flustra foliacea (Linnaeus, 1758). However, only some alkaloids have shown to be active against tumour cell lines until now. Chartellines A-C and chartellamides A-B were isolated from C. papyracea in the Roscoff region of France, being the first examples of polycyclic indole alkaloids in marine bryozoans. Chartelline A, the first compound isolated from this species with a penta-halogenated indole containing a β-lactam ring, was inactive against leukemia cells in the NCI’s test . Three new halogenated, hexacyclic indole-imidazole alkaloids, securamines H-J, together with the previously reported compounds securamines C and E were isolated from the Arctic bryozoan S. securifrons collected off the coast of Hjelmsøya (Norway). . Securamines C, E and H-J were evaluated for their cytotoxic activity against human cancer cell lines A2058 (skin), HT-29 (colon), and MCF-7 (breast), as well as against non-malignant human MRC- 5 lung fibroblasts. Securamines C, E, H and I were found to affect cell viability, being H, I and E the most potent, with IC 50 values ranging from 1.4 ± 0.1 to 10 ± 1 µM . While a crude extract of F.
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Being a retrospective analysis, this study has several limitations. The absolute number of patients was relatively small, so small differences, such as for the relationship between age and cancer laterality, were not statistically apparent. Incomplete information regarding family history in many patients may cast doubt on the validity of the conclu- sion reached. Such incomplete information was related to poor communication between some patients and their rela- tives, and inability to remember the relevant details concern- ing family members who died many years earlier. However, this study has significance despite those limitations. Its main strength is the inclusion of all consecutive breast cancer
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Abnormalities of Wnt genes were regulated carcinogenesis, and 19 Wnt genes have been the specialized role in cancer development. Each Wnt gene plays a crucial impact in each cancer type 5 . Abnormalities of Wnt genes regulated vast cancer development such as breast cancer, endometrial carcinoma, pancreatic adenocarcinoma, prostate cancer, leukemia, melanoma, lung carcinogenesis, medulloblastoma, gastric carcinoma, colorectal adenocarcinoma, esophageal squamous cell carcinoma, Basal cell carcinoma, oral squamous cell carcinoma, head and neck squamous cell carcinoma, bladder cancer, teratocarcinoma, ovarian carcinogenesis and non-small cell lung cancer 3, 4 .
Jeroen Veldman (henceforth JV): OK, thank you Samuel and hello everybody. Where I’m going to make a distinction is on this question of corporate nature. I’ve regularly asserted that, historically speaking, the corporation has only recently come to be spoken of as a private entity (Beverungen et al., 2014). From around the 13 th century until the beginning of the 19 th century, it was understood as a solely public entity. At the end of the 18 th century, after the French revolution, the corporate form is radically revised: when you no longer have kings, you can’t have a concession (see Maitland, 2003). Because people now pay to get a concession from a state consisting of individuals who get to determine who gets a license and who does not, the accusation of corruption is never far away (see Bowman, 1996). This was one of the main arguments to open up the concept of incorporation to all individuals and for all purposes, allowing the use of this special legal concept for private purposes. Subsequent innovations are the attribution of ownership to a separate legal entity, the automatic attribution of limited liability from the middle of the 19 th century, and the idea that one separate legal entity can ‘own’ and buy or sell another one by the end of the 19 th century.
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In summary, our work has uncovered a likely causal variant in the TERT-CLPTM1L Region 2 susceptibility locus and identiﬁed ZNF148 as a potential effector of a gene-regulatory element that mediates increased TERT expression in an allele-speciﬁc manner. Furthermore, our ﬁne-mapping results highlight the complexity of this region and indicate that Region 2 may, in some cancers, consist of more than one underlying functional signal. Our results are remarkably consistent in eight cell lines across four different cancer types and explain, at least in part, the biological underpinnings of risk for rs36115365. Notably, our data suggest that the mechanism by which ZNF148 inﬂuences TERT is similar for cancer types in which the C-allele of rs36115365 contributes to increased risk, or alternatively to disease protection. Although TERT expression and ensuing effects on telomere length may be the crucial underlying mechanism in mediating inverse risk for different cancers, studies of surrogate tissue telomere length and cancer risk have been contradictory and shown associations with short or long telomeres, or no effect 45–53 . TERT could also mediate risk through its telomere-independent functions that include transcriptional regulation and mitochondrial RNA polymerase activity (for review see Martinez et al. 54 ). Other factors may contribute to the pleiotropic effects observed for rs36115365, including differential environmental exposures, regulatory effects through genes beyond TERT, interaction with additional risk variants and/or somatic mutations both within Region 2 and the larger TERT/CLPTM1L locus, or tissue-speciﬁc regulation of ZNF148 and other transcription factors mediating TERT expression. Our ﬁndings represent the ﬁrst steps in unravelling the complex functional consequences of carrying risk variants in Region 2 of chr5p15.33 and strongly indicate a major role for expression of TERT in inﬂuencing risk of multiple cancer types.
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The concept of credit for business was alien to Nigeria until the establishment of banking institutions Century. Prior to the growth in trading activities from about 1861 in Lagos, of illegal trafficking in persons and minor trading in basic consumer goods. The stoppage of slave trade made British merchants to shift to trading in raw materials like rubber, bauxite, iron for their nascent factories. Borrowing for agrarian products or existent except for seedlings for land which was super abundant. Borrowing therefore was considered anathema or fraudulent and failure to repay loans usually resulted in slavery, ostracism, confiscation of wife and children of the defaulter. With the oil boom, businesses imbibed corrupt and extravagant practices, coupled with general illiteracy, tribalism, nepotism which affected business performance and loan repayment. It is not unusual for loans or other funds for unproductive activities like politics and for acquisition of more wives and ostentations living. This paper seeks therefore to trace the history of corporate borrowing in Nigeria within the local cultural milieu. Attempt has also been made to differentiate between the various types of receiverships, and the continued influence of equity rules. Also, the nature and basic powers of a receiver are analysed as there is still great confusion e legal status of a receiver is examined to ascertain the reality and pragmatism of their neutrality in the discharge of their functions. In addition, the courts