Cell lines that have been conditioned to become resistant over time in this way are very valuable because they mimic what happens in patients who stop responding to therapy. They help us find out how cancer cells changed when they became resistant, and test whether new drugs will work in resistant as well as sensitive patients. Some cancers become resistant by switching on special survival proteins when they sense danger. One such protein is PI3K, which is activated when cancer cells are attacked by a drug. PI3K, once activated, goes on to activate other proteins that have other effects that help cells survive under stressful conditions.
Drugs are being designed to block this kind of chain reaction. For example, last year a clinical trial showed that a drug called Afinitor could potentially thwart resistance caused by the PI3K pathway in some cancers, by blocking the action of one of the chemicals in this pathway. One such protein is called P-gp, and it evolved as a way to protect us against infection.
Its normal function is to push pathogens such as bacteria out of our cells before they have a chance to make us ill. Scientists have been trying to block the action of the P-gp pump for decades, but it has turned out to be difficult to interfere with it without harming the patient. I hope his documentary about Dr. Sebi still sees the light of day… he was doing such great work … unbelievable timing. This happened to Nipsey Hustle right before this Dr.
Sebi documentary …wake the fuck up smh. He was Working on a documentary for Dr. Sebi the doctor who claimed he could cure aids and who was executed because his aids cure would mess up the U. Oh what a coincidence huh!? Nipsey got killed just before he could expose the government in his upcoming documentary about Dr.
Sebi… who died mysteriously after claiming to have the cure for AIDS pic. Dr Sebi cures cancer, gets trailed and dies from a mysterious cause of death… Nipsey decides to make a documentary about Dr. However, smoking is a risk factor for incisional hernia, and it has been shown that smokers have a 4-fold higher risk of incisional hernia development It has also been reported that smoking is a risk factor for recurrence after groin hernia repairs, possibly due to abnormal connective tissue metabolism in smokers On the other hand, smoking has not been found to be a risk factor for recurrence of umbilical 36 or inguinal hernias Like obesity, smoking does not seem to be a common etiologic factor for cancer and hernias; moreover, the intersection points are more obscure.
Estrogen is a well-established risk factor for many types of cancer, particularly breast and endometrial cancer Today, the effect of estrogen on tendons and ligaments is not well-understood Estrogen may inhibit the local inflammatory response and impair wound healing In a clinical study on fibroblasts retrieved from recurrent hernia patients, it has been shown that estradiol has no influence on the impaired type I to type III collagen ratio As early as , Hazary and Gardner reported that male mice given estrogen for prolonged periods developed inguino-scrotal hernias A very recent study by Zhao et al.
Tamoxifen is a commonly used selective estrogen receptor modulator that has been used for hormonal treatment of breast cancer for a long time now 68 , Its side effects and potential risks have been well-studied in women The potential side effects in men are infertility and gynecomastia Ma et al. These interesting findings create an intersection for hernia and cancer and future studies could provide more surprising results on this topic.
Regarding mutual causation, there is no evidence and even no argument about cancer development secondary to any hernia. However, as discussed below, a low-grade contention has been upheld suggesting that the prosthetic material used for hernia repair induced carcinogenesis. On the contrary, abdominal wall hernias may develop not because of the cancer itself but due to its consequences, for example increased intra-abdominal pressure secondary to an obstructive colon cancer or a large pelvic tumor may cause herniation.
The necessity for colorectal cancer screening in patients with inguinal hernia will be discussed in an upcoming part of this review. Genetic factors may have a role in the etiology of both cancer and abdominal wall hernias. The first studies on a genetic factor for hernias were published in the s 73 , In , Gong et al. They found that persons with indirect inguinal hernias might have inherited a gene, more frequently from their father.
In the new millennium, genetic studies on inguinal hernias have gone much further. A Swedish study revealed that a positive family history of hernia surgery was a risk factor for abdominal wall hernias Some of these genetic alterations may also play a role as etiologic or prognostic factors in human cancers Jorgenson et al. They found four novel loci for the etiology of hernia development. Wang et al. The same group also reported that EFEMP1 promotes ovarian cancer cell growth and metastasis 85 , and is a potential diagnostic biomarker for prostate cancer WT1 gene, although it is a suppressor gene in kidney tumors, acts as an oncogene in leukemia, lung cancer, breast cancer, and glioblastoma Although we can see some intersections for hernia and cancer above, none of these findings means very much today.
Therefore, it is not possible to make any statement about a possible etiologic factor. However, new clues could arise from newer genetic studies on abdominal wall hernias. This has been an interesting field where researchers aimed to identify a particular biomarker for the prediction of abdominal wall hernia development. A recent Dutch study found that advanced glycation end products AGEs might be used as a biomarker for incisional hernia. Measurements based on the use of a Skin Auto Fluorescence SAF reader revealed that AGEs were significantly higher in patients with incisional hernia than in the control group AGEs are harmful compounds generated by non-specific glycation of proteins and lipids which are related to cardiovascular diseases, arteriosclerosis, and neurodegeneration Likewise, they may have a possible role in cancer initiation and progression They have been thought to promote a breast cancer cell line by enhancing proliferation, invasion, and migration Another animal study demonstrated that there might be a link between AGEs and lung cancer Rosch et al.
Calaluce et al. They revealed an association between GREM1, a bone morphogenetic protein antagonist 1, and incisional hernia formation. GREM1 was underexpressed in skin and fascia of patients with recurrent hernia compared with control subjects. Although GREM1 might promote carcinogenesis 98 , its expression has also been shown to be associated with a good prognosis in gastric and colorectal cancers 99 — As presented above, while at least some direct and indirect evidence has been obtained for certain biomarkers in hernia formation and for the relationship between these markers and cancer, it is not possible to demonstrate a link between hernia formation and carcinogenesis.
Further studies may or may not change the picture in the future.
An international, multicenter study group named ColoCare has been recruiting colorectal cancer patients to identify biologic markers to predict clinical outcomes In one of their studies they researched predictive biomarkers for incisional hernia development after cancer surgery Some proteins including RNA polymerase III transcription factor, calreticulin, estrogen receptor 1, and Harvey rat sarcoma viral oncogene homolog were found to be higher in cases of postsurgical incisional hernia.
Furthermore, in gene set analysis, melanoma, bladder cancer, focal adhesion, pathways in cancer, etc. Although there is a certain relationship between these proteins and cancerogenesis — , this does not mean shared or similar etiological mechanisms for hernia development and cancer. In fact, many proteins and genes play complex roles in cancer biology; the same substance may have both promoter and inhibiter effects on different levels of cancerogenesis and metastatic disease.
Integrins are the main receptor proteins that cells use to bind to the extracellular matrix , Integrins are involved in many pathological conditions such as inflammation and tumor progression This also works against metastasis , Moreover, the blockade with DisBa may be preventive against incisional hernia development.
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A recent animal study from Brazil demonstrated that DisBa increased the number of macrophages and fibroblasts and no subject treated with this recombinant disintegrin developed incisional hernia The authors concluded that this might be a promising therapeutic tool in wound healing and incisional hernia prevention. In fact, these findings may not only present a hope for lower incisional hernia rates in the future but may also reflect a common etiological factor for cancer and a type of abdominal hernias. Till today, no series has been published revealing a high incidence of any cancer type in patients with abdominal wall hernias, or vice versa.
However, there are reports of a correlation between inguinal hernia and testicular cancer. Earlier reports on this topic were very close to implicating childhood inguinal hernia in the development of testicular tumors. In , Morrison reported that the testicular cancer risk was almost three times higher in men who had had an inguinal hernia than in those who had not, with no association seen between the side of hernia and side of tumor Coldman et al.
They found that the probability of testicular tumor was higher in patients with inguinal hernia. That effect was even greater in the presence of concomitant cryptorchidism. In fact, congenital inguinal hernia is secondary to incomplete obliteration of the processus vaginalis, whereas an undescended testis is another aspect of the same process.
This might indicate a common etiology. A UK study also reported that inguinal hernia was a risk factor for testicular cancer; hernia repair before the age of 15 years was a risk factor for seminoma Likewise, a USA study reported that a hernia operation after age 7 years presented a significantly elevated risk of testicular cancer In , the United Kingdom Testicular Cancer Study Group reconfirmed that testicular cancer may be associated with inguinal hernia One year later, Gallagher et al. Nevertheless, just after, two case-control studies from Denmark stated that inguinal hernia was not a risk factor for testicular cancer in the absence of cryptorchidism or testicular atrophy When we evaluated more recent data, a study from the Slovak Republic revealed that inguinal hernia was one of the most prominent risk factors for testicular cancer As a bottom line, we can say that the relationship between the testicular tumors and inguinal hernia is definitely a point where the roads of cancer and hernia intersect.
Raymond C. Starting from the changes in collagen metabolism in patients with hernias, he stressed the biochemical evidence available for the extracellular matrix ECM in patients with colonic diverticulosis.
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He cited Schumpelick et al. Indeed, an Aachen group scrutinized this subject and published several related papers, however, they never mentioned any pathways involving hernia disease. Later, Filik and Biyikoglu wrote a letter to Read's editor and agreed with him on a possible preventive effect of diverticulosis against colonic cancer Nevertheless, no objective findings have been presented to date about the protective effects of hernia disease against cancer.
- Made in 1985;
- Incidence and epidemiology!
Another topic related to the above one is the difference in incisional hernia rates after surgery for diverticulitis and cancer. Pogacnik et al. The authors speculated that several factors including collagen tissue disorder might play a role for this finding. Prasad et al. Very recently, Tang et al.
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