scholarly journals A new hypothesis: some metastases are the result of inflammatory processes by adapted cells, especially adapted immune cells at sites of inflammation

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 175 ◽  
Author(s):  
Leili Shahriyari

There is an old hypothesis that metastasis is the result of migration of tumor cells from the tumor to a distant site. In this article, we propose another mechanism for metastasis, for cancers that are initiated at the site of chronic inflammation. We suggest that cells at the site of chronic inflammation might become adapted to the inflammatory process, and these adaptations may lead to the initiation of an inflammatory tumor. For example, in an inflammatory tumor immune cells might be adapted to send signals of proliferation or angiogenesis, and epithelial cells might be adapted to proliferation (like inactivation of tumor suppressor genes). Therefore, we hypothesize that metastasis could be the result of an inflammatory process by adapted cells, especially adapted immune cells at the site of inflammation, as well as the migration of tumor cells with the help of activated platelets, which travel between sites of inflammation.  If this hypothesis is correct, then any treatment causing necrotic cell death may not be a good solution. Because necrotic cells in the tumor micro-environment or anywhere in the body activate the immune system to initiate the inflammatory process, and the involvement of adapted immune cells in the inflammatory processes leads to the formation and progression of tumors. Adapted activated immune cells send more signals of proliferation and/or angiogenesis than normal cells. Moreover, if there were adapted epithelial cells, they would divide at a much higher rate in response to the proliferation signals than normal cells. Thus, not only would the tumor come back after the treatment, but it would also grow more aggressively.

2020 ◽  
Vol 13 (03) ◽  
pp. 2050021 ◽  
Author(s):  
Sachin Kumar ◽  
Abdon Atangana

Cancer belongs to the class of diseases which is symbolized by out of control cells growth. These cells affect DNAs and damage them. There exist many treatments available in medical science as radiation therapy, targeted therapy, surgery, palliative care and chemotherapy. Chemotherapy is one of the most popular treatments which depends on the type, location and grade of cancer. In this paper, we are working on modeling and prediction of the effect of chemotherapy on cancer cells using a fractional differential equation by using the differential operator in Caputo’s sense. The presented model depicts the interaction between tumor, normal and immune cells in a tumor by using a system of four coupled fractional partial differential equations (PDEs). For this system, initial conditions of tumor cells and dimensions are taken in such a way that tumor is spread out enough in size and can be detected easily with the clinical machines. An operational matrix method with Genocchi polynomials is applied to study this system of fractional PDEs (FPDEs). An operational matrix for fractional differentiation is derived. Applying the collocation method and using this matrix, the nonlinear system is reduced to a system of algebraic equations, which can be solved using Newton iteration method. The salient features of this paper are the pictorial presentations of the numerical solution of the concerned equation for different particular cases to show the effect of fractional exponent on diffusive nature of immune cells, tumor cells, normal cells and chemotherapeutic drug and depict the interaction among immune cells, normal cells and tumor cells in a tumor site.


1923 ◽  
Vol 38 (5) ◽  
pp. 591-604 ◽  
Author(s):  
James E. McCartney ◽  
Peter K. Olitsky

In our experience, covering a large number of rabbits, we have found that the condition known as snuffles falls into different types, the acute and fatal, symptomatic of some underlying infection such as septicemia or pneumonia; and the intermittent, and the chronic. The intermittent and the chronic types considered in this paper are those most commonly present in laboratory stocks. Our observations point to a widespread prevalence of the disease among rabbits kept under laboratory conditions. This statement might be questioned had the stock we examined been derived from a single source. But the animals were procured from dealers who obtain rabbits in New York, Pennsylvania, Ohio, and as far west as Michigan. The same dealers supply the stock of most of the laboratories in the East. Hence we believe that this disease is found generally prevalent in this part of the country. We have demonstrated that practically all rabbits with intermittent or chronic snuffles reveal old chronic inflammatory processes of the upper nasal passages associated with thick inspissated pus in one or more sinuses. Moreover, these conditions are also present in about one-tenth of carefully selected, supposedly normal stock rabbits and in one-fourth of a casually selected group, free, during long periods of observation, from any of the symptoms of active snuffles. The peculiar anatomy of the animal's nose which predisposes to the ready formation of enclosed pockets of purulent material may be the cause for the chronicity of upper nasal affections. When the animal's resistance is lowered, the long standing, inflammatory process can flare up into an acute exacerbation, and then show itself as typical snuffles. Various means can effect this: chilling the body, the intravenous injection of foreign proteins such as killed vaccines, or the intranasal inoculation of microorganisms of divers species. Bacteriological examination of the nasal secretions or sinus pus from animals with snuffles and those apparently free of the disease shows the presence in both cases of various microorganisms—Staphylococcus albus, Bacillus bronchisepticus, Bacillus lepisepticus, and others, in order of frequency. Different bacteria may be found in different sinuses in the same animal. A lack of recognition of these factors has led, we believe, to erroneous conclusions with regard to the inciting agent of the disease. Bacillus lepisepticus and Bacillus bronchisepticus have been declared the incitants of snuffles. Our experiments, in which an attempt was made to induce the disease de novo with these microorganisms, failed. In all cases (with a single exception) in which snuffles followed, there was evidence of an infection which, judging from the condition of the nasal passages and from the cells in the exudates or secretions, had existed before the inoculations were made. Furthermore, the microorganisms recovered from the nasal passages had as a rule no relationship to those in the material inoculated. We attempted also to produce snuffles by inoculating intranasally the unfiltered and filtered suspensions of the ground nasal mucous membranes from typical cases of the disease occurring in stock rabbits. These attempts also failed. It appears, therefore, that intermittent and chronic snuffles, as it attacks rabbits kept under laboratory conditions, is, as a rule, a sign of an underlying condition—an exacerbation of a chronic inflammatory process in the upper nasal passages, associated with a purulent paranasal sinusitis. The microorganisms recovered are to be looked upon as tending to maintain such conditions but we have still been unable to reproduce typical snuffles with them, employing supposedly normal stock rabbits for the purpose. One may presume that some agent, as yet undetermined, diminishes the resistance of the nasal mucosa, allowing different bacteria to invade and multiply there, thus causing disturbance. In this respect perhaps an analogous condition exists to that which prevails in epidemic influenza and common colds in man. It is obvious that further work along these lines cannot be properly carried out with rabbits whose antecedent history is unknown. The problem of the incitant of snuffles can best be studied in a breeding stock which is well controlled, one affording an opportunity to observe the animals from an early period of life.


2020 ◽  
Vol 21 (1) ◽  
pp. 3-10
Author(s):  
Denis Dmitrievich Bolotov ◽  
Alexey Alexeevich Novikov ◽  
Sergey Bolevich ◽  
Nina Aleksandrovna Novikova ◽  
Andrey Vladimirovich Yakovchenko

AbstractChanges in the body in the presence of a chronic inflammatory process, even of a low intensity, lead to the change in the body’s reactivity, having a negative impact on the development, course and clinical prognosis of newly emerging inflammatory processes. Structural changes in the vascular network in the focus of chronic inflammation and following cellular reactions that occur under the action of chemokines and cytokines are the basis for the maintenance and development of the phlogogenic process, including subsequent structural changes in tissues. The failure to resolve the inflammation leads not only to the persistence of the process in the primary focus, but also to the formation of a multitude of the so-calledpathological circles, included at the system level, causing the imbalance among proinflammatory, anti-inflammatory and pro-resolving factors. As a result, conditions are formed for the emergence of new foci of the inflammation in other organs and tissues and in the case of their realization, new vicious circles are formed that contribute to the maintenance and progression of the inflammation. The complex application of etio-tropic, pathogenetic and sanogenetic principles of the treatment allows intensifying of the formation of specialized pro-resolving factors with the elimination of their relative insufficiency, contributing to the reduction of newly formed vessels and to the restoration of the normal cellular composition of the tissue as well as to the resolution of inflammation.


2017 ◽  
Vol 01 (02) ◽  
pp. 096-099
Author(s):  
Omar Zurkiya ◽  
Suvranu Ganguli

AbstractViral oncolysis broadly refers to the use of modified viruses to infect and subsequently lyse tumor cells. This concept arises from the observation that viral replication is itself effective in destroying tumor cells. This effect is then amplified by reinfection of adjacent tumor cells by the progeny virion released from lysed tumor cells. Herpes simplex virus 1 (HSV-1) has been the primary focus of current efforts in viral oncolysis. It is a double-stranded DNA virus that is a ubiquitous pathogen transmitted by direct mucosal contact. HSV-1 possesses several features well suited to viral oncolytic therapy. It does not integrate into the cellular genome, has a large transgene capacity of up to 50 kb, and is already highly prevalent in the general population. In addition, effective antiherpetic agents are available to stop unwanted viral replication. HSV-1 mutants that preferentially replicate in neoplastic cells rather than normal cells have been characterized, and several variants of replication deficient HSV-1 mutants have been created and studied. They follow a common theme in that their replication is significantly attenuated in normal cells, while activated in cancer cells. Studies have been performed in various strains including those known as G207, NV1020, talimogene laherparepvec, and rRp450, and are reviewed here. Viral oncolysis is an exciting area of research with applications to tumors throughout the body. It holds promise as a new treatment for primary and metastatic liver cancer and may soon become a relevant therapy in interventional oncology.


1953 ◽  
Vol 97 (5) ◽  
pp. 651-662 ◽  
Author(s):  
Jean V. Cooke ◽  
David Goldring ◽  
Lawrence I. Kahn

Observations are reported on the changes which occurred in excised rabbit and human skin after mild trauma and incubation at body temperature. These changes resembled those of chronic inflammation, in that perivascular and diffuse infiltration by histiocytes occurred in the corium and subcutaneous tissue, but they developed within a few hours. The experiments have shown that even after removal from the body certain tissue elements may retain the ability to react with proliferative changes in response to tissue injury if kept under artificially simulated physiological conditions. The possible significance of these changes in relation to the inflammatory process is discussed.


2020 ◽  
Vol 16 (3) ◽  
pp. 30-36
Author(s):  
Elena Semencova ◽  
Vladimir Bazarnyy ◽  
Yuliya Mandra ◽  
Larisa Polushina ◽  
Elena Svetlakova

Subject. With increasing age of patients, in many cases, the severity of periodontal diseases also increases, and dystrophic ones join the inflammatory processes. Local predisposing factors in the oral cavity are aggravated by concomitant somatic diseases and a decrease in compensatory processes against the background of physiological aging. Literature data indicate that the manifestations of the physiological process of aging and pathological processes (inflammatory and dystrophic) can be clearly observed on the example of buccal epithelial cells. The aim is to identify the relationship between the age of patients, their periodontal status and the cytological characteristics of buccal epithelial cells. Methodology. All study participants were divided into two groups: the first included patients with a conditionally healthy periodontium (72 people), the second - with a chronic inflammatory process in the periodontium (57 people). In accordance with the WHO classification, a gradation of age was carried out: young (18―44 years old), mature (45―59 years old), elderly (60―74 years old), senile (75―90 years old). All patients underwent a comprehensive dental examination, sampling and cytological examination of the buccal epithelium, calculation of the integral indices of the buccal cytogram. Results. In healthy patients, a weak positive correlation was established between the cytogenetic index, the index of the accumulation of cytogenetic disorders and age, a weak negative correlation was found between the proliferative index and age. In patients with an inflammatory process in the periodontal tissues, a multidirectional change in the values of the buccal cytogram indices was observed, which may indicate an imbalance in the processes of regeneration, apoptosis, and cellular damage in inflammatory periodontal diseases in older age groups. Conclusions. In patients with healthy periodontal disease, a regular accumulation of cytogenetic disorders occurs with increasing age, while proliferative activity, on the contrary, decreases. Patients with inflammatory phenomena in the periodontal tissues are characterized by imbalance, impaired coordination of regeneration and apoptosis processes, combined with the most pronounced reactivity in the middle age period.


Author(s):  
Feng Zhang ◽  
Runmin Jiang ◽  
Chao Zhang

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na+/K+ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na+/K+ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na+/K+ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.


2020 ◽  
Vol 27 ◽  
pp. 00080
Author(s):  
Orazali Mullakaev ◽  
Viktor Usenko ◽  
Irina Konstantinova ◽  
Elvira Bulatova

Pathomorphological study of the neonatal period piglets of ontogenesis from the pig breeding complex obtained from sows that were given feed contaminated with mycotoxins during pregnancy and after parturition was carried out. Pathological changes in the internal organs of piglets, characterized by various dystrophic and inflammatory processes resulting from the influence of mycotoxins, were established. Edema and congestion in the lungs of piglets is noted as a sign of circulation failure in the body. Signs of interstitial pneumonia are detected with areas of chronic alveolar emphysema and atelectasis. Signs of granular dystrophy were noted in the heart in cardiomyocytes. Interstitial connective tissue has signs of edema; the swelling of blood vessel walls is noted. The morphofunctional state of the thyroid gland in piglets, taking into account changes in the organ structure, is characterized as a macro-microfollicular proliferating colloid goiter. The border smoothness between white and red pulp, hyperemia of blood vessels and the small number of lymphatic nodules with a size decrease are noted in the spleen. The demarcation clarity of white pulp into separate structural zones is not diagnosed in lymphatic nodules. Signs of catarrhal enteritis and chronic catarrhal colitis with a tendency to its transition to atrophic catarrh are detected in the small and large intestines of the gastrointestinal tract. Hepatocytes have mild signs of granular dystrophy in the lobules of the piglets’ liver. Protein hepatosis signs interspersed with areas of necrobiosis are identified in separate lobules of the organ against the background of general atrophy of hepatocytes. Granular dystrophy signs with the phenomena of its desquamation in certain areas are revealed in the convoluted tubules of kidney nephrons in epithelial cells. Part of epithelial cells of the nephron tubule is subject to necrobiotic processes. Thickening of the basic capillary membrane with glomerulitis is noted in the glomerulus of the renal corpuscle. Edema and mild lymphocyte-macrophage infiltration with the phenomena of the mucoid swelling of blood vessel walls is observed in the interstitial organ tissue.


Mathematics ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 1285 ◽  
Author(s):  
Sana Abdulkream Alharbi ◽  
Azmin Sham Rambely

Changes in diet are heavily associated with high mortality rates in several types of cancer. In this paper, a new mathematical model of tumor cells growth is established to dynamically demonstrate the effects of abnormal cell progression on the cells affected by the tumor in terms of the immune system’s functionality and normal cells’ dynamic growth. This model is called the normal-tumor-immune-unhealthy diet model (NTIUNHDM) and governed by a system of ordinary differential equations. In the NTIUNHDM, there are three main populations normal cells, tumor cell and immune cells. The model is discussed analytically and numerically by utilizing a fourth-order Runge–Kutta method. The dynamic behavior of the NTIUNHDM is discussed by analyzing the stability of the system at various equilibrium points and the Mathematica software is used to simulate the model. From analysis and simulation of the NTIUNHDM, it can be deduced that instability of the response stage, due to a weak immune system, is classified as one of the main reasons for the coexistence of abnormal cells and normal cells. Additionally, it is obvious that the NTIUNHDM has only one stable case when abnormal cells begin progressing into early stages of tumor cells such that the immune cells are generated once. Thus, early boosting of the immune system might contribute to reducing the risk of cancer.


2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
T Gossler ◽  
F Ricklefs ◽  
T Deuse ◽  
E Masuda ◽  
V Taylor ◽  
...  

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