Connection of Cancer to Microbes - Research Paper Example

Cancer is a disease in which cells go through abnormal development process and obliterate contiguous tissues and may broaden to other body locations. This results in damage of DNA. There are some warning signs through which cancer existence in a person can be envisaged. But for proper recognition and diagnosis of this fatal disease, biopsy organism’s mirco study is needed. . Infectious bacteria play an important role in causing cancer disease. Some of the common bacteria microorganisms which can cause cancer are Strepcoccus Bovis, Salmonella typhi and Helicobacter pylori. Cancer can be caused in different regions of body like carcinoma is a skin cancer, lymphoma and myeloma is originated in cells of immune system and sarcoma is linked to bones and muscles. Cancer of colon, lungs and liver are severe and result in a large number of deaths each year. Introduction: It was general thought of physicians in the last century that bacteria could also be a reason for cancer disease in the same way as it was responsible for diseases like leprosy, tuberculosis and syphilis. At that time, cancer coccidian, sporozoons and cancer parasites were from those discovered microbes which when injected into animals resulted in cancer tumors. But later this concept was proved to be incorrect because these microbes were only capable of damaging the tissues after the formation of cancer. In 1890 William Russell, a well known pathologist of his time, noted that sphere-shaped structures were present in histopathologic sections of cancer and he entitled it as “characteristics organism of cancer.” Later, these organisms were identified as microbial forms. However, in the start of 20th century a successful research revealed the existence of bacteria in breast and other cancer varieties. Nuzum also did research on microbe and conducted few experiments. In one of his test he induced breast cancer bacteria in aged man’s groin and after several inductions skin cancer was produced. This meant that different kinds of cancer could be caused by breast cancer bacteria. In the mid of 20th century Livingston studied deeply about cancer microbes. The basic characteristic of the organism was that it could exist in different forms and sizes. The biggest form was similar to cancer parasite discovered by Russell. The middle sized microbes were analogous to mycoplasma, cell-wall deficient forms and L-forms and the smallest bacterial creatures were like virus. According to Livingston, these microbes were linked to mycobacteria which were responsible for tuberculosis. She named this organism Progenitor cryptocides. As said by Livingston, all human beings consisted of cancer organisms in their tissues, blood and body liquids. These microbes remained in active until the human body is working normally but they became active due to irregularities in immune system, causing heart disease and cancer. During the same time period, Irene Diller proved that these bacteria were responsible for causing cancer by refining the microbes from cancer tumors which she created by injecting cancer bacteria in animals (Cantwell, “Killer Microbes” ). Ignorance of medical profession on Cancer microbe research: Regardless of microbe research over a hundred of years, bacteria-cancer relationship is ignored by the medical line. But the discovery of stomach bacteria in 1982 is an exemption because now medical professionals admit that the stomach bacteria can cause stomach ulcers which may result in gastric cancer and lymphoma. Ewing argued that infectious disease and cancer were not alike because he was unaware pleomorphic (i.e. different forms and sizes) characteristic of cancer microbes results in organisms having features of both bacteria and viruses (Cantwell, “Acid-Fast Bacteria”). BACTERIA AND CARCINOGENESIS 15% of worldwide malignancies are expected to be ascribed as infections like virus, bacterial and schistosomes. The link of bacteria to melanoma is more considerable as compared to viral infectional which are related to cancer. One of the compelling testimonies is the link of gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma with Helicobacter pylori. Other species and cancer associations are Salmonella typhi with gallbladder cancer, Streptococcus bovis with colon cancer and Chlamydia pneumoniae with lung cancer. 17 million cases per annum of gallbladder cancer have been noted down worldwide and from these 90 percent cancer species are adenocarcinoma. Recent researches have showed that Salmonella typhi is one of the major factors of gallbladder cancer and it increases the risk to 8.47 times. Never-ending infections can be caused by bacteria and it can also make cell growth tainted by disturbing the cell cycle. The consequential injure to DNA is analogous to the genes distorted control of normal cell division and apoptosis caused by carcinogenic agents. The result of cellular control distortion and loss is tumor instigation and the later outcome of this cell growth restriction is further alterations and increase in cell control loss. Breaking away of cells from tumor and starting tumor at remote sites is the most dangerous effect. Bacterial infections like reactive oxygen species (ROS), interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and nitric oxide (NO) through the stimulatory and mutagenic effects of cytokines contribute to carcinogenic changes and if the environmental factors like smoking is present then their contribution is momentous (Mager). Colorectal cancer and infection: 1. colorectal cancer and enterococcus faecalis: An experiment was carried out to examine the relationship of colorectal cancer and bacterial infection. Dove detected that tumor development in mice which were born and upholded in germ free environment was half in contrast to those mice which were kept under specific pathogen-free conditions. The polyp formation in germ free environment mice was increased by the removal of myeloid differentiation factor 88 (myd88) adapter proteins, a main moderator of the tlr/interleukin, which means that bacteria use tlr-mediated signaling mechanism for colorectal cancer development. The finding of human-bacteria communication associate micro biota as important factor of colorectal cancer. The existence of bacteria is informed by the Toll-like receptor (tlr) and the Nod-like receptor to the host. In intermittent human colorectal cancer (CRC), intestinal commensals make large contribution but pertinent microorganisms have not been recognized due to complex bionetwork of intestine. There is linkage of bacteria and gastrointestinal tumorigenesis; for instance, Helicobacter pylori is regarded as class I carcinogen for gastric cancers. Human colon consists of more than 400 microorganisms with more than 1011 colony-forming units (cfu) per gram of feces and medical science is still unsuccessful to cultivate and characterize 75% of these species. Therefore, focusing on commensals, which are potentially mutagenic and can grant long term revelation to the host, is adopted as an alternative approach. One of the small components of intestine microorganisms is Enterococcus faecalis. It is an uncommon bacterium that can injure colonic epithelial DNA and can produce reactive oxygen species (ROS) as well as extracellular superoxide. It can also be a reason for irritation and colorectal cancer in interleukin-10 unconscious mice and enhances chromosomal instability (CIN) in mammal cells. In solid tumors, the most general type of genomic unsteadiness is CIN and it contains increase and decrease of complete or parts of chromosomes followed by reversal, translocations and complex reorganizations in the genome chain and structure. Aneuploidy characterizes these unsteady alterations in genomic content for cells with CIN. According to mathematical representation, CIN occurs earlier in tumorigenesis but CIN origin is vague. Through mechanisms started by superoxide, E.faecalis advance CIN. Creation of clastogens and promotion of cyclooxygenase-2 (COX-2) in macrophages results in distortion of DNA. E. faecalis–infected macrophages produce clastogens and the process is equivalent to the stimulation of CIN through the radiation induced bystander effect. This effect arises in vivo in congenic sex-mismatch bone marrow transplantation experiments and is produced on the activation of cells by radiation which damage DNA of cells which are in neighborhood and are not radiated. Due to the large involvement of innate immune cells to tumorigenesis through prostaglandins, cytokines, and chemokines, macrophage-induced bystander effect becomes steady. DNA double-strand break down, G2 arrest and alteration in chromosome number are associated with superoxide generation. These were the result of bystander effect which provides a proper method of cellular transformation and tumorigenesis by involvement of redox-active intestinal commensals. 2. Colrectal Cancer and Strepcoccus Bovis Streptococcus bovis (S. bovis) bacteria is interrelated to colorectal cancer and have very adverse effect on human health. S. bovis biotype I constructed 94% of S. bovis bacteremia which was linked with colorectal cancer while biotype II made 18% implication. The pathogenesis of several inflammatory diseases, for example Crohns disease or ulcerative colitis, could be associated with intestinal bacteria which resulted in the examination of local host-microbe and gastrointestinal commensal flora connections. Infections and inflammation results in cancer and the brawniest interaction of unceasing irritation with cancer are inflammatory bowel diseases of colon. Research has shown that carcinogenesis cause cannot be slandered to single microorganism, but some particular bacterium can play a key role for damaging mutagens; for instance, transformation in tumor suppressor genes is caused by bacterial methyltransferases. Further research demonstrated that the key means of mutations in normal colorectal mucosa might be cytokine-based sequel of bacterial inflammation. In the colonic mucosa of rats, S. bovis/gallolyticus bacteria extremely amplified the construction of inflammatory cytokines which might result in colorectal cancer. Chronic irritation can result several dangerous changes like bacteria-induced cancer formation can be caused by Host genetic polymorphisms of the adaptive and instinctive immune reaction. Inflammation plays a vital role in growth of gastrointestinal cancers. Antigens extracted from S. bovis wall to numerous cells, including human colonic cancer cells (Caco-2), produced inflammatory cytokines by those cells. These antigens are supporter of cancer because when they are stimulated in vitro over expression of cyclooxygenase-2 (COX-2) which endorse cellular proliferation and angiogenesis through prostaglandins and reduce apoptosis. NF-κB and IL-8 transformations play an important role for S. gallolyticus succession of colorectal adenoma to carcinoma because NF-κB can enhance carcinogenic effect and IL-8 can put forth promulgating effect on colorectal mucosal cells. Cell transformation and the rate of genetic mutations can be boosted by MAPKs which is generated by S. bovis/gallolyticus proteins. These MAPKs, especially p38 MAPK, can provoke COX-2 which is a significant aspect of tumorogenesis. Thus S. bovis/gallolyticus bacteria participation in development and proliferation of all types of human cancer is considerably high (Abdulamir, Hafidh and Bakar). MICROBIAL PATHOGENS AND MALT LYMPHOMA 1. MALT lymphoma An ordinary low grade B-cell lymphoma which begins due to chronic inflammatory disease is Mucosa-associated lymphoid tissue (MALT) lymphoma. The chronic inflammatory diseases are originated by microbial pathogens and these microorganisms are important factor for malignant transformation and subsequent clonal expansion of the transformed clone. H. pylori caused gastric MALT lymphoma growth which escorted to successful treatment of lymphoma with antibiotics (Du). 2. Campylobacter jejuni and immunoproliferative small intestine disease (IPSID) Mucosa-associated lymphoid tissue (MALT) is a small intestine tissue in which Immunoproliferative disease occurs which is a type of lymphoma. Another name for it is alpha chain disease because it is linked with appearance of a single type truncated immunoglobulin alpha heavy chain without being coupled with light chain. A tri-step molecular approach has been followed to relate immunoproliferative small intestinal disease with C. jejuni infection. In the first observation biopsy specimens of the proximal small intestine was acquired from the patient before the commencement of antimicrobial treatment. These specimens were used to prepare PCR assay by using universal bacterial 16S rDNA primers and DNA templates. It gave rise to amplicons encircling the whole 16S rDNA gene that were recognized as C. jejuni by sequencing. In this step other enteropathogens were not perceived. In the second observation, C. jejuni was confirmed in infected biopsy specimens by immunohistochemical analyses and Fluorescence in Situ Hybridization. The following picture shows Fluorescence in Situ Hybridization (FISH) and Immunohistochemical Analysis of Tissue specimens Third experiment was the linkage of fast reduction of immunoproliferative small intestinal disease with the abolition of C. jejuni by antimicrobial therapy. The demonstration of monocentric series of archival biopsy specimens resulted in four campylobacter-associated disease cases in six patients having immunoproliferative small intestinal disease. Puri illustrated that C. jejuni diarrhea was developed in a patient after two to three days of treatment of antineoplastic chemotherapy for immunoproliferative small intestinal disease. Secretion of CdtB poison that intervene damage to DNA and Continuation of C. jejuni was observed in Peyers patches and mesenteric lymph nodes in a gnotobiotic mouse model. In pathogenesis of immunoproliferative small intestinal disease, these characteristics could be dangerous. Sturdy IgA mucosal response and unceasing infection can be extracted from C. jejuni because it supports continuous promotion of mucosal immune system. The ultimate result of this stimulus can be IgA-secreting clones expansion and assortment of a replica that exudes heavy chains that has evaded antibody-antigen Fc-dependent down-regulation. The relationship of C. jejuni and immunoproliferative small intestinal disease recognition can help to diagnose, control, and avoid this disease (Lecuit). 3. Borrelia burgdorferi and cutaneous marginal B cell lymphoma Lyme illness which is linked with unrelieved skin cancer is caused by Borrelia burgdorferi. Several explorations have been carried out to show the existence of Borrelia burgdorferi in primary cutaneous B-cell lymphoma. The occurrence of Borrelia burgdorferi is more in marginal zone B-cell lymphoma than other forms of lymphoma and it relapse totally on antibiotic treatment. Vanishing of the specie is followed by drastic decrease in plasma cells and CD3+ T cells. This research is an evidence of Borrelia burgdorferi support antigen-driven development of cutaneous marginal zone B-cell lymphoma. Association between Chlamydiae Psittaci infection and Ocular Adnexa Lymphoma: 80% of the ocular adnexal lymphoma case patients consisted of Chlamydia psittaci DNA. There is also a link between Chlamydiae species and neoplastic diseases. These species cause unrelenting infections which are mutagenic in vitro, stimulate polyclonal cell propagations in vivo, and confrontation to apoptosis in infected cells. In a study which was conducted to observe the C. psittaci and Ocular Adnexa Lymphoma relationship, it was noted that 50% patients with Chlamydia-positive lymphomas at diagnosis contained observed C. psittaci DNA in the PBMCs. This research supports the existence of C. pneumonia DNA in circulating cells of humans and the assumption that never ending infections could be supported by a prolonged C. psittaci infection in PBMCs. C.psittaci is eliminated by doxycycline treatment due to which lymphoma deterioration occurs. This study is a proof for C.psittaci infection and of ocular adnexal lymphomas development linkage. The following image shows immunocytochemical studies in ocular adnexal lymphoma samples (Ferreri). Mycoplasma hyohinis and Cancer Relationship The undeviating ways for the development of different types of cancer are still unknown but as a common assumption Mycoplasma hyorhinis infection is considered a major cause for different categories of cancer like gastric cancer. Mycoplasma hyorhinis infection is illustrated in cancer, cervical condyloma tissues and ovarian cancer using PCR and enzyme-linked immunosorbent assay (ELISA). Several scientific studies revealed that mycoplasma genitalium and mycoplasma hyorhinis infections stimulate malignant transformation of human prostate cells BPH-1 and increase migration and invasion. In addition to this, p53 activation is abridged by mycoplasma infection; NF-κB is set in motion and is cooperated with oncogenic Ras in the transformation of rodent fibroblast. p37 which is present on Mycoplasma hyorhinis membrane as a part of homologous, high-affinity transport system, augments tumor cell attack in vitro, restrains mammalian cell from sticking together, and persuade secretion of TNF-α from human peripheral blood mononuclear cells. In short, it is not wrong to say that tumor cell gathering, migration and incursion can be endorsed by Mycoplasma hyorhinis and p37 interceded Mycoplasma hyorhinis infection and support cell migration. By the induction of EGFR phosphorylation and enhancing MMP-2 activity, p37 can possibly encourage gastric cancer cell invasion and metastasis (Yang). Conclusion DNA is distorted by the unrestrained development of abnormal cells is termed as cancer disease. Pathogenic bacteria, especially those which result in relentless infections, can endorse unusual cell growth by evasion of immune system or stifling apoptosis. Survival of intracellular pathogens is due to escaping the capability of the host to recognize them as foreign. There are several bacterial organisms linked with cancer but the infections caused by these species have familiar characteristics. It takes several years for cancer growth as examined in the cases in which cancer is related with H. pylori, S. typhi and S. bovis infections. Carcinogenesis can be caused and promoted by the involvement of unceasing interactions between infective specie and immune response and a vulnerable host. Cancer can be prevented by the treatment or prevention of the infections. Works Cited 1. Abdulamir, Ahmed S., Rand R. Hafidh, and Fatimah A. Bakar. "The association of Streptococcus bovis/gallolyticus with colorectal tumors: The nature and the underlying mechanisms of its etiological role." Journal of Experimental and Clinical Cancer Research (2011): Web. 30 Apr. 2011. 2. Cantwell, Alan R. "Acid-Fast Bacteria In-Vivo in Prostate Cancer and the Connection between Prostate Cancer, Other Cancers, and the Kaposi’s Sarcoma Virus." JOURNAL OF INDEPENDENT MEDICAL RESEARCH (2004): n. pag. Web. 1 May 2011. 3. Cantwell, Alan R. "Do Killer Microbes Cause Breast Cancer? Suppressed and Forgotten Research Could Hold the Key to a Cure for this Dread Disease."Aries Rising Press (2003): n. pag. Web. 1 May 2011 4. Du, Ming-Qing. "MALT Lymphoma:Recent Advances in Aetiology and Molecular Genetics." J Clin Exp Hematopathol 47.2 (2007): n. pag. Web. 1 May 2011. 5. Ferreri, Andres J., et al. " Evidence for an Association Between Chlamydia psittaci and Ocular Adnexal Lymphoma." Journal of National Cancer Institute 96.8 (2004): Web. 1 Jan 6. Lecuit, Mark, et al. "Immunoproliferative Small Intestinal Disease Associated with Campylobacter jejuni." The New England Journal of Medicine (2004): Web. 30 Apr. 2011. 7. Mager, DL. "Bacteria and cancer: cause, coincidence or cure? A review." Journal of Translational Medicine(2006): n. pag. Web. 30 April 2011. 8. Yang, Hua, et al. "Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells." BMC Gastroenterology (2010): Web. 1 May 2011. Read More