Fully agree. But it is not only the swamp. It is the mosquito and the swamp.

Because in the case of cancer it is the mosquito who creates the swamp.

Fully agree. But it is not only the swamp. It is the mosquito and the swamp.

Because in the case of cancer it is the mosquito who creates the swamp.

The swamp is already there when tumor is completely developed. For this reason, it is hard to say that only cancer is preparing tumor microenvironment (swamp). And we still do not clearly know the interaction between cancer and its microenvironment / macroenvironment (whole system). Targeting only cancer cells do not work. Because microenvironmental and systemic changes are still there.

In my opinion, at the beginning we should stop the engine that drives cancer (i.e. destroy the mitochondria of cancer cells). Then, we can try to "dry the swamp".

Heterogeneity is a hallmark of tumor. Relapse always occurs from a little of mutant cells which are diffrent from primary tumor cells and difficult to be detected. So it is important to understand tumor heterogeneity clearly and inhibit these cells proliferating in the colony sites.

decreasing cancer genetic heterogeneity by destroying of cancer cell mitochondria...?

A good comparison. If the cancer cells are mosquitoes, then any maskat has a predecessor; bloodworm (larva). This larva can be in the swamp for a long time, and can even survive the drought and, under rain and favorable conditions, give a new mosquito.

Dear friends

Thanks for your contriution.I want to share this interesting study

Genetic changes help mosquitoes survive pesticide attacks

...

For decades, chemical pesticides have been the most important way of controlling insects like theAnopheles mosquito species that spreads malaria to humans. Unfortunately, the bugs have fought back, evolving genetic shields to protect themselves and their offspring from future attacks.

The fascinating array of genetic changes that confer pesticide resistance in Anopheles mosquitoes is reviewed in an article published today in Trends in Parasitology. The paper is written by Colince Kamdem, a postdoctoral scholar, and two colleagues from the Department of Entomology at the University of California, Riverside. The findings highlight the interplay between human interventions, mosquito evolution, and disease outcomes, and will help scientists develop new strategies to overcome pesticide resistance....

from

Article Human Interventions: Driving Forces of Mosquito Evolution

(like cance?)

Mosquitoes have external problems, but cancer has internal problems to solve... - "Mitochondria Help Cancers Grow": http://jonlieffmd.com/blog/mitochondria-help-cancers-grow

Dear Andrzej

Thanks for your reply,

Is it important?( Mosquitoes have external problems, ) I think, our major aim MUST BE saving our field(body)

Dear Mesut,

In my opinion, the reason for adaptation/development is important:

- toxic environment (chemical pesticides) - external problem of mosquitoes to solve (i.e. how to adapt),

- diseased mitochondria - internal problem of cancer to solve... (how to escape???)

Good question!

I'm aware that there was Malaria in the Valencia region, Spain, in the 40s and 50s, how they eradicated it, I don't know.

In cancer therapy, many are using both approaches, think in use of Bevacizumab, a blocker of vessel growth, in abdominal malignancies promoting ascites, along with chemotherapy to kill malignant cells.

The exact doses and better combination and timing of CT and Anti-Angiogenic therapy is probably not yet fully defined.

Toxicity and cost issues matter too, the QALY cost is always hovering above patients, as a vulture.

Regards. Salut +

The swamp can be partially or fully created by a low-grade inflammation present in the body. It would be nice to see a comparison of the presence of cancer in people having or without present inflammation in the body.

Inflammation can be caused by diet (sugars, starches, trans-fats, food additives, low-level infectious diseases, etc.).

It is known that diet has a great impact on healing cancer. Is anybody trying to go in this direction in clinical research? It is cheap, easy, and safe.

There is no doubt that cancer micro-environment is important however, defining the mosquito to destroy to me seems the more pertinent question.

Cancers are usually a heterogeneous mixture of cells expressing an or multiple aberrant cellular differentiation pathways, but like mosquitoes in malaria it is not the majority of these cells that kill, it is the continued survival and spread of cancer stem cells (malaria infested mosquitoes) which ultimately leads to death in malaria and cancer patients, respectively.

Thus like the male mosqiuito that does not bite, not all cancer cells are equivalent targets.

I come from a slightly different, epigenetic perspective. We have found that BMI-1, originally identified as an oncogene, is highly expressed in cancer stem cells relative to the more differentiated general tumor cells. BMI-1 is the E3 ubiquitin ligase catayltic subunit of PRC1, which along with PRC2 and DNA methylation are responsible for the aberrant silencing of genes involved in many aspects of cell identity, signalling and proliferation in most cancers (Gieni and Hendzel 2009). The Retinoblastoma, Ink/Arf, p53 integrated cell cycle arrest process is made ineffective through either mutation or epimutation; i.e., in this case the aberrant silencing of genes which impact cell cycle arrest and apoptosis, in almost all cancers.

Silencing of non-tissue appropriate genes is the primary way in which cells define and protect identity. In Cancer and regular Stem cells many developmental pathways are bound by both repressive and gene expression activating complexes leaving them in a repressed yet inducible state. As cells differentiate many of the tissue inappropriate genes become permanently silenced allowing terminal differentiation and eventual cell death. Within a tumor most of the cancer cells are carrying out this sort of pathway made inappropriate by the introduction of both mutations and epimutations, however, the rare cancer stem cells remain undifferentiated and more mobile. Our major contribution was to show that ubiquitylation of Histones by BMI-1 is one of the very earliest steps in the DNA Damage Response (DDR) providing the initial ubiquitinylations required for creation of poly ubiquitin chains which activates the DDR cascade of repair factors.

These initial ubiquitinylations are now found to be responsible for the gene silencing that occurs in the genes found both up and down stream of double strand breaks potentially creating the conditions for further aberrant gene silencing events.

One of our major contributions has been to show that the high level of BMI-1 expression in cancer stem cells provides enhanced DDR function, in effect protecting the CSC from the very DNA damaging treatments meant to destroy them. This makes sense in the context of regular stem cells where the protection of DNA sequences is paramount to the stem cell properly carrying out developmental gene expression but is a means of cellular protection in the CSC. Thus shrinkage of a tumor after such therapy is only ultimately effective if the CSC population self-protected from such damage is also eliminated.

BMI-1 is one of a handful of "stemness genes" whose high expression in tumors is shown to define a "death from cancer" phenotype in a large range of cancer types ( Glinsky et al. 2005). Its contribution appears to be at numerous levels including over activation of cellular signalling pathways through silencing of negative regulators, silencing apoptosis and cell cycle arrest related genes, to protection of CSC from DNA damaging therapies.

There is also debate about the origin of CSC. Indeed, epithelial to mesenchymal transition is a normal physiological process of de-differentiation required for many functions, which reactivates "stemness associated genes" within epithelial cells resulting in more "CSC like" gene expression pattern. The process of dedifferentiation of even well differentiated cell types such as fibroblasts back to pleuripotent stem cells, and the many examples in the literature of various combinations of manipulations which can result in re-initiation of a stem cell expression phenotype suggests that the story of the origin of mosquito; the CSC and their self-renewal abilities is still being defined.

This is very interesting analogy, cancer = mosquito. From my own experience, grew up in tropical country with all sorts of bloodsucking insects living all around us, malaria is one of them. In general, people living in jungles or rural areas seem to have a tendency to develop resistance against malaria, or other types of musquito-related diseases. My wild guess is that, this is something to do with the diets as well as the ability of body to develop certain amount of immunity against certain diseases - the later might be due to human evolution. Reports are abundant telling us that several antioxidants and many other stuffs derived from natural plants, could prevent cancer, diabetic, etc. One way to treat cancer, maybe try to find certain chemicals which can triger the body immune system to produce itntermediate chemicals which then can destroy cancerous cells.This approach is a bit different from the conventional one, where in the conventional case, e.g., an external chemical is used to destroy the cancerous cells. But in this approach, the external chemical does not destroy the cancerous cells directly, but it trigers the body itself to manufacture certain chemicals, which can destroy the cancerous cells. This is just a 1 cent idea, of course.

..... These failures may result from focusing on therapeutic killing of mutant cancer cells without integrating the restoration of microenvironmental interactions that naturally participate in repressing malignant phenotypes.

from

Stromal directives can control cancer

Science  12 Jul 2019: Vol. 365, Issue 6449, pp. 122-123 DOI: 10.1126/science.aaw2368

But who will kill mosquitoes and dry the swamps!

All recent innovative approaches to kill and dry these things fails if the workers inside the body fail to support these operation. What i meant by worker is the immune system. Take for example, immuno-check point inhibitors have succeeded to double survival in patients with melanoma, NSCLC ..etc. But this comes only with one condition; the immune system is working well and infiltrating the tumor micro-environment. Thus, in most treatment protocol where immune check point could be use, you find that a positive PD1 expression or lymphocytes infiltration is a condition for their use.