blogger.com is a platform for academics to share research papers. (PDF) Bates’ Guide to Physical Examination and History Taking 12 ed | Marvin Gómez - blogger.com blogger.com no longer supports Internet Explorer The average quality score at our professional custom essay writing service is out of The high satisfaction rate is set by our Quality Control Department, which checks all papers before submission. The final check includes: Compliance with initial order details. Plagiarism. Proper referencing Examples Of Breast Cancer Research Papers Ln, Business Plan Template blogger.com, Best Laptop For Homework , Kcl War Studies Dissertation
(PDF) Bates’ Guide to Physical Examination and History Taking 12 ed | Marvin Gómez - blogger.com
Try out PMC Labs and tell us what you think. Learn More. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, examples of breast cancer research papers ln, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.
In the yearHanahan and Weinberg published their influential review: the hallmarks of cancer [ 1 ] henceforth termed Hallmarks I where they attempted to organize the dense complexities of cancer biology into six major hallmarks: self-sufficiency in growth signals, insensitivity to anti-growth signals, evading apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. A decade later, an updating review [ 2 ] henceforth termed Hallmarks II added two emerging hallmarks: reprogramming energy metabolism and evading immune response, and two enabling traits: genome instability and mutation, and tumor-promoting inflammation.
Although in Hallmarks I the authors anticipated that over the following decade cancer research would undergo a process of simplification where less layers of complexity are added, Hallmarks II arrived at such a decade mark with conversely daunting complexities. We have seemingly come full circle: from overwhelming complexity to anticipated simplicity, back again to substantial complexity-a perspective that was highlighted by Weinberg himself [ 3 ].
Nevertheless, the reviews have managed to persist at the core of the cancer biology literature, serving as blueprints for understanding the core traits of cancer. We would add that even invasion and dissemination are properties of certain non-malignant conditions, an example of which is endometriosis, a relatively-common condition among females in which endometrial cells migrate to extra-anatomical sites and invade new tissues, all while maintaining a benign histological appearance [ 5 ], examples of breast cancer research papers ln.
We argue, however, that the goal of the hallmarks is providing an organizational framework of cellular properties uncovered during the transformation of phenotypically normal cells-whether such a transformation stops at a benign growth stage or continues in the direction of a more evolved and threatening malignancy.
It is clear that even the initial hallmarks list contains tissue-relevant rather than cancer-cell-specific components e. angiogenesis [ 1 ] and Hallmarks II has a section dealing with the tumor microenvironment TME [ 2 ]. More recently, phenotypically normal cells were shown to carry a high burden of non-silent somatic mutations that are positively selected upon without the formation of cancer [ 10 - 12 ].
Furthermore, the stromal component of tumors has proved to be an occasional initiator [ 1314 ] and an indispensible accomplice [ 15 ] of the cancer process. We do believe that continuing to expand on SMT to encompass newer realizations while having a concurrent tissue view rather than abandoning it is best for the time being-at least until inevitable progress in systems biology presents us with a more comprehensive model.
The attempts at classification of somatic mutations into driver and passenger has helped such conceptual expansion [ 16 ]. We are also examples of breast cancer research papers ln to see beyond the genes through the appreciation of the significant role of epigenetics in the cancer process [ 17 ].
Finally, the stromal compartment of tumors has been a subject of great dissection in the recent years [ 15 ], examples of breast cancer research papers ln. A final critical point would be whether the description of the hallmarks has led to translational benefit in the clinic [ 67 ]. In Hallmarks II, various drug categories were linked to their targeted hallmark, but many have proved to only be effective for a limited time or within limited settings.
There is referral to the important concept of shifting hallmark dependence during therapy [ 2 ]. Indeed, viewing the hallmarks as individual, segregated, and static targets is insufficient; the complementarity of the hallmarks, their codependence, and the evolutionary dynamics governing them are essential considerations [ 6 ].
And with this current work, we aim to draw a more organized, robust, and updated picture of such hallmarks. The transformation process. Different insults continuously act on cells leading to transformative alterations in epi genetics, chromosomal numbers and arrangements, and heterotypic interactions which, along the path towards malignancy, undergo cycles of evolutionary clonal selection leading to the acquisition of cancer-competent traits, the hallmarks of cancer.
Normal cells depend on growth signaling of a tightly-regulated cell cycle to controllably proliferate and maintain tissue homeostasis-this is disrupted in case of cancer [ 2021 ]. It is currently appreciated that in cancer cells, the growth and proliferative signaling pathways harbor one or more driving alterations within their compartments giving them a survival edge [ 16 ].
Those compartments include growth ligands, their receptors or the cytosolic signaling molecules. While often the case, the distinction remains a virtual one. Take examples of breast cancer research papers ln growth factor-β TGF-β as an example, this conventional anti-growth ligand has been conversely shown to be implicated in tumor-progression both by stimulating cancer-cell de-differentiation [ 22 ] and reshaping the TME [ 23 ].
The receptors binding these ligands may also be altered in various manners, e. But perhaps the most common alterations are encountered in the downstream compartment. Such signaling networks are complex and still under investigation. Downstream cascades mediate RAS functions, prominently the RAF-MEK-ERK and the PI3K-AKT-mTOR networks, the components of which could independently be mutated in a similar fashion in various types of cancer.
Importantly, mutations in RAS, its regulatory proteins, or its downstream networks result in a examples of breast cancer research papers ln of effects beyond enhanced growth and proliferation that include suppression of apoptosis, rewiring of metabolism, promoting angiogenesis, and immune evasion, and thus reflect examples of breast cancer research papers ln fact that a single signaling cascade could be implicated in multiple hallmarks of cancer [ 29 ].
Even in the presence of growth signaling, tight regulation of the cell cycle via regulatory proteins keeps the division cycles in check. For cancer cells to grow, deregulation of the cell cycle and checkpoint disruption are crucial [ 21 ].
One key regulator is the retinoblastoma RB protein, commonly inactivated in a multitude of malignancies [ 30examples of breast cancer research papers ln ]. As is the examples of breast cancer research papers ln with RAS, it has been shown that the RB family are not limited to proliferative control, but are involved in multiple roles-impinging on various other hallmarks-that include maintenance of genomic stability, examples of breast cancer research papers ln, regulation of apoptosis, cell metabolism, senescence, angiogenesis, examples of breast cancer research papers ln, and suppression of invasion and metastasis [ 3032 ].
P53 acts as a stress detector and responder, being sensitive to a variety of stresses that include genotoxic stress, excessive signaling, nutrient deprivation, and hypoxia. Arresting further proliferation, p53 is then involved in initiating repair mechanisms, or if the damage is beyond repair, initiating cell death or terminal differentiation states [ 3536 ]. The molecule has also been linked to metabolic rewiring, regulation of autophagy, and redox homeostasis [ 35 ].
This, also again, is not representative of the full picture where, for example, examples of breast cancer research papers ln, a great percentage of one tumor type e. pancreatic adenocarcinoma could carry driving mutation s in the labeled oncogene compartment alone [ 16 ].
Furthermore, such compartmental labeling is merely artificial; in reality, a context-dependent interchange of functions is seen in different tumor settings and at different stages of tumorigenesis [ 37 - 39 ].
On their journey towards examples of breast cancer research papers ln malignancy, cancer cells face a wide range of stresses that include excessive signaling, DNA damage, hypoxia, nutrient scarcity, and even anticancer therapy.
Physiologically, examples of breast cancer research papers ln, cells adopt a variety of responses to adapt examples of breast cancer research papers ln the stress if possible or, when the stress is overwhelming, altruistically be eliminated for the sake of healthy whole tissue. These mechanisms are subverted in cancer cells for the outcome of their overall survival and propagation Figure 2. Metabolic response is elaborately discussed under Hallmark E, and we will discuss some of the other stress responses relevant to the cancer setting.
Altered stress response. Different stressors act on different compartments of normal and to a higher degree cancer cells. Some of the stress responses are subverted or hijacked for overall survival on the road towards malignancy.
CM: Cell Membrane, R: Receptor, C: Cytosol, N: Nucleus containing DNA, M: Mitochondria. The cell employs a multitude of repair pathways as part of the wider DNA damage responseeach composed of a variety of molecules working cooperatively to amend a specific type of DNA lesion. The need for cumulative, driving, unrepaired genetic insults persisting mutationstogether with the unstable genetic makeup of most tumors, logically implicate defects in repair machinery in the story of tumorigenesis.
Some of the most notable familial cancer syndromes entail germline mutations involving DNA repair genes [ 42 - 44 ]. Acquired cancers have also been shown to exhibit defects in repair pathways as they evolve [ 45 ], and polymorphisms involving repair genes have been correlated to cancer risk; those are probably further responsible for variability of therapeutic response since most anti-cancer therapies function by inducing DNA damage [ 4647 ].
Perhaps counterintuitive is that overexpression of various repair proteins has also been observed in tumors; for example, upregulation of RAD51 has been demonstrated in leukemia, breast, and pancreatic cancers [ 48 ].
Such upregulation is linked to increased therapeutic resistance and post-treatment relapse [ 4849 ]. Thus, DNA repair pathways are best considered multidimensional regulators in the cancer context, the disruption of which over-reliance on an upregulated pathway or defects in another serves overall tumor survival and progression, but may also represent a vulnerability that could be exploited for therapeutic purposes [ 4049 ].
Another response to transformation-associated stress, including irreparable DNA damage, uncontrolled proliferation, or matrix detachment, involves apoptotic cell death [ 5051 ]. In cancer, the balance between cell proliferation and cell death that normally maintains healthy tissue homeostasis is disturbed [ 51 ]. The extrinsic pathway to apoptosis involves the interaction of cell surface receptors with their ligands. The more-relevant intrinsic pathway involves sensing of internal stress levels compatible with apoptosis, a shift of balance favoring pro-apoptotic over anti-apoptotic proteins, and mitochondrial outer membrane permeabilization MOMP with release of activating molecules from the intermembrane space.
Both pathways converge on activation of caspases, cleavage proteins efficiently completing the task of cell death within minutes [ 51 - 53 ]. Cancer cells are able to surpass apoptotic response by various mechanisms [ 5153 ]. Inactivating mutations involving p53 render the cell insensitive to many apoptotic stimuli although, and fortunately, pindependent cell death pathways exist.
Upregulation of anti-apoptotic or loss of pro-apoptotic proteins through epi genetic means occur in various tumors. Cancer cells also occasionally inhibit caspase activity even with the occurrence of MOMP. It is important to note that, although the net outcome of those alterations is enhanced tumor survival, this does not mean that all cells within a tumor are insensitive to apoptotic signals. Contrarily, tumor cells are likely to be more sensitive to apoptotic stimulation than normal cells and apoptosis is continuously occurring in growing tumors [ 5556 ].
In fact, apoptosis could serve an evolutionary role under conditions of selective pressure by eliminating less-fit lineages, evacuating a niche for predominance of better-suited clones and contributing to cancer progression [ 54 ]. Autophagy macroautophagy, the most widely described type is a recycling process of intracellular components that physiologically serves a quality-control function, operating at a low basal rate, removing pathologic long-lived or misfolded proteins and damaged organelles [ 57 ], and may also be involved in unconventional protein secretion [ 58 ].
It is upregulated as a protective response to a variety of stresses that include pathogenic, metabolic, and genotoxic ones [ 59 ].
The tumor-suppressor aspects of autophagy were described early on [ 60 ]. Engineered mice with homozygous loss of the beclin encoding an essential autophagy protein died during embryogenesis, while those haploinsufficient developed spontaneous tumors with examples of breast cancer research papers ln [ 6162 ].
The mechanisms by which autophagy suppresses tumorigenesis are still elusive, but may include selective elimination of damaged mitochondria during periods of stress reducing the burden of reactive oxygen species ROSmetabolic homeostasis, degradation of overexpressed proteins, sharing in immune surveillance, and serving as a defense line against potentially-carcinogenic bacteria and viruses [ 596364 ]. On the other hand, evidence has implicated autophagy in tumor survival and progression; upregulated autophagy and even autophagy dependence is a feature of many malignancies [ 63 ].
Autophagy may conversely enable cancer cells to survive harsh metabolic stress and hypoxia, evade immune-surveillance, acquire invasive and metastatic characters, or secrete Examples of breast cancer research papers ln proteins [ 585965 ], and thus represents another stress response with context-dependent roles in different tumor settings and stages, liable for hijacking for overall tumor survival [ 63 ]. Another defense mechanism against cellular stress is senescence: the process of irreversible exit from the cell cycle [ 66 ].
On critical shortening of telomeres after exhaustion of replication potential, examples of breast cancer research papers ln, induction of senescence occurs; successive divisions would lead to cycles of chromosomal fusion and breakage, resulting in genomic instability and allowing accumulation of potentially-transforming alterations [ 6667 ].
Short telomeric length is almost a universal feature of halted benign and pre-malignant lesions [ 6869 ]. Consequently, such halt needs to be bypassed in fully transformed cells. A variety of other stresses can also induce senescence: non-telomeric DNA damage e.
that caused by ROS or anti-cancer therapystrong, long-lasting, or unbalanced mitogenic signaling, and activation of tumor-suppressors, all consistent with the cytoprotective role of senescence [ 6668 ]. The passive role of senescent cells has, however, been challenged in the recent years, mainly through the characterization of senescence-associated secretory phenotype SASP : soluble signaling factors, insoluble proteins and matrix components, and proteases released by senescent cells, capable of reshaping the microenvironment surrounding them [ 6671 ].
Contrasting beneficial e. Tumors cannot grow beyond mm 3 nor metastasize without new vasculature [ 73 ]. Although angiogenesis is the most discussed, various other modes of tumor vascularization exist with redundancy in usage, partly explaining resistance towards antagonizing a single mode [ 74 ].
We choose to adopt the latter terminology. Angiogenesis is the process of sprouting, cell division, migration and assembly of endothelial cells ECs from pre-existing vessels [ 75 ].
It is utilized during embryogenesis for expansion and remodeling of primitive vascular networks, and is part of postnatal events including wound healing, examples of breast cancer research papers ln, the female reproductive cycle, and chronic inflammation [ 76 ]. In these events, however, angiogenesis is turned off or may be prolonged but self-limiting, unlike in case of malignancies where the process is continuously activated.
Only when a trigger tips the balance towards pro-angiogenic factors as in case of malignancy is the switch turned on and do vascular-quiescent tissues show signs of angiogenesis [ 77 ]. The most important trigger of angiogenesis is hypoxia.
ECs possess a number of oxygen-sensing mechanisms, chiefly those interfacing with the hypoxia-inducible transcription factor HIF family, regulating the expression of a multitude of genes not only involved in angiogenesis, but in cell survival, metabolism, and inflammation as well.
Responding to hypoxia, stabilized HIF initiates an adaptive transcriptional response, many products of which are factors involved in turning on the angiogenic switch [ 7879 ]. With hypoxia being a feature of tumors, it is not surprising that HIF levels are higher in many cancers, correlating with poor clinical prognosis [ 80 ].
New Insights on Breast Cancer Research
, time: 2:34ScholarAssignments - Best Custom Writing Services
Feb 01, · Few examples of drug-target networks analyses show that both simvastatin and ketoconazole are anti-proliferative compounds in breast cancer, while gene expression profiles suggest that topiramate can be used to treat small-cell lung cancer and that sirolimus can be useful for glucocorticoid-resistant acute lymphocytic leukemia. On the other An essay is a short piece of writing, and it needs to have the correct level of quality matching your readers’ interests. If you fall short in your essay writing task, then it will make your readers disappointed, and at the same time, you will be getting a low score for an essay C.T.C. Arsene, P.J.G. Lisboa, in Outcome Prediction in Cancer, 1. INTRODUCTION. Survival analysis is an important part of medical statistics, frequently used to define prognostic indices for mortality or recurrence of a disease, and to study the outcome of treatment. The books by Kalbfleisch and Prentice (), Lawless () together with the more recent ones by Lee (), Collett
No comments:
Post a Comment