Infectious Agents and Cancer

Infectious Agents and Cancer

Human herpesvirus 8 (HHV-8) DNA sequences have been detected in Kaposi’s sarcoma, in primary effusion lymphoma (an unusual high-grade non-Hodgkin’s lymphoma seen primarily in patients with acquired immunodeficiency syndrome [AIDS]), and in Castleman’s disease (a rare lymphoproliferative disorder); however, proof that HHV-8 is involved in the pathogenesis of these diseases remains to be established. The alteration of the cellular genome after a carcinogenic exposure may result in malignancy if apoptosis is prevented and the immune surveillance fails to eliminate the transformed cell. Traditionally, these studies focused on gonorrhea or syphilis. Epidemiologic studies on this topic could play important roles in answering both old and new questions, which could augment current knowledge and open new areas of research. Several studies evaluate cancer risk in Africa, a region heavily affected by the HIV/AIDS epidemic. NETs from other entities, however, were negative for all HPyVs. Also important are the molecular mechanisms whereby viruses interact with the immune system and the immune evasion strategies that have evolved.

In situ hybridization indicated that mRNAs for v-cyclin D and kaposin, an HHV-8 latency-associated gene, were present in approximately 1% of the spindle cells in early patch lesions and approximately 60% of the spindle cells in late nodular lesions of Kaposi’s sarcoma. Conclusions: Spindle cells of Kaposi’s sarcoma, which have been regarded as the tumor cells of this cancer, contain v-cyclin D mRNA. According to the National Cancer Institute, Hodgkin’s lymphoma (HL) accounts for 4 − 6% of all childhood cancers, with the highest incidence rates in 15–19 year olds [2]. Cell lines established from these secondary tumors also expressed ORF74 and were tumorigenic. There are other subtypes of childhood NHL, but they account for less than 5% of all cases. The second beta sheet in the S20-3 peptide stabilizes the loop, but at the same time, it decreases loop flexibility and increases bulkiness of the peptide, limiting its access to the K1 binding site in the presence of the K1 protein. Neuroblastoma is diagnosed in 7% of the CC cases, nephroblastoma (Wilms) tumors occurs in 5% and retinoblastoma in 3% CC cases [2].

Cancers found in children are usually quite distinct from those seen in adults. Because the causes of childhood cancers are unknown, it is difficult to determine a specific mechanism. Filters were washed and further incubated for 1 hour at room temperature with a 1:1000 dilution of peroxidase-conjugated anti–mouse immunoglobulin G (Sigma). In this review, we address the possible role of infectious agents in the onset and progression of childhood tumors. To date, in addition to inherited factors, the World Health Organization (WHO) classifies four different groups of external agents as carcinogens which cause cancer in children. These are physical, biological, chemical carcinogens, and dietary components (e.g., cured meats) [5]. Antibodies against the open-reading frame 73 (LANA) were tested by a similar ELISA using full-length baculo expressed LANA as antigen and serum diluted 1 : 100.

Blood samples were taken from these two patients and added to a new Guthrie card. All serum samples were sent frozen for laboratory analysis at the Centro di Riferimento Oncologico in Aviano, Italy, where they were analysed by immunofluorescence for the presence of HHV8 antibodies by experienced laboratory personnel. In general, in 5 − 15% of CC cases genetic factors are thought to predispose the child to the development of cancer [7]. Indeed, 10–15% of the cancers worldwide, or over 1.3 million cases of cancer each year resulting in almost a million deaths, can be linked to viral infection (Parkin, 2006). Because cancer is a multifactorial disease caused by genetic and environmental factors, it is often difficult to determine the critical period of exposure as during pregnancy or earlier [9]. In contrast to the oncogenicity and tumorigenicity of its viral genome, KSHV infection of ECs leads to the induction of KS markers, spindle cell phenotype and signs of transformation but does not result in the acute angiogenicity and tumorigenicity characteristic of KSHV-infected spindle cells in lesions. Two models have been proposed to explain how infectious agents could play a role in the development of childhood leukemia.

The first model relies on the direct transforming ability of transforming viruses. Because HSV-1 resides in neurons during latency, cells within the brain that can mediate immune responses are key in controlling HSV infection and spread. In this case, the action of microorganisms may be indirect and non-transforming (reviewed in [11]). One of the main agents in the proposed infectious association with childhood leukemia is a group of human herpesviruses, especially Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). Associations of EBV with childhood leukemia, mainly lymphoblastic leukemia (ALL), have been found in some seropositivity studies, genetic analyses, and epidemiological studies. However, it is unable to bind nectin-2 but binds CD155 instead (17,–19). Epidemiological studies of HBV infection and HCC in the 1970s associated HBV with the development of HCC, and clear-cut epidemiological evidence of an etiological role was published in 1981 (29).

However the statistical significance of the results was not confirmed by a larger study of the same group [13]. The presence of VCA antibodies is recognized as a sensitive measurement for active infection. While for EBV reactivation, testing for ZEBRA and for EBV early antigen antibody was found to be useful. In addition, ZEBRA IgG and VCA IgM antibody associations were attributed to increased risk of non-ALL in offspring. EBV ZEBRA protein interacts with mitotic chromosomes, and with p53 and promyelocytic leukemia proteins. This might suggest a proposed mechanism for the transforming activity of the virus. Recent DNA studies show that latent membrane protein 1 of the EBV gene transcripts was found in 29/80 of the cancer cases versus 0 in the control group, in cases of ALL, AML, and chronic myelogenous leukemia (CML) [14].

C. In the study positive controls (patients with Burkitt’s lymphoma and infectious mononucleosis) were consistently positive, but healthy donors, other disease controls, cases of AML and multiple myeloma showed negative results [15]. There are several mechanisms by which EBV could increase the risk of malignant transformation of infected cells. We further analyzed these NETs for the presence of DNA from 12 AAVs, adeno virus-5, 27 HPVs, HBV, and XMRV. About 5% develop chronic infections, which can cause chronic active hepatitis and cirrhosis (17). Analyses of HHV-8 gene expression. Information has been reported on possible roles of HHV-6 in leukemia development (reviewed in [35]).

HHV-6 was first isolated from patients with lymphoproliferative disorder. In some experiments, naked DNA (10 μg) was injected intramuscularly in 0.2 ml of sterile phosphate-buffered saline (PBS) in a 25-gauge needle. [36] showed that HHV-6 antibody level was increased in children with ALL, but a subsequent study showed no significant difference (50 patients/50 controls). Slight but significant serological correlation was shown in case control studies with AML. The presence of HHV-6 IgM in 40% of children with leukemia, and high avidity of IgG compared with controls was shown in further studies. HHV-6 DNA was found in bone marrow cells of children with T-cell ALL. Importantly, a direct transforming ability of HHV-6 was shown in vitro with 3T3 cells and human epidermal keratinocytes.

HHV-6 also has a unique ability to integrate viral DNA into chromosomes. Chromosomal transmission of HHV-6 DNA was shown in ALL cells in culture (reviewed in [35]). Apart from integration into chromosomal DNA, HHV-6 protein products are also able to interfere with host protein functions. U95 binds to NF-kB, altering the pathway, and U14 and ORF-1 bind and inactivate p53 [30]. These interactions likely contribute to the oncogenic transformation of infected host cells. The fact that neither HHV-6 DNA nor EBV were detected in dried blood spots obtained from newborns at birth indicates that congenital infections with these viruses are uncommon. Antibodies against herpes simplex, another member of the Herpesviridae, were prevalent in children with ALL in Iran.

Patients had higher values of antibodies against HSV1 IgG (82.2%) comparing to a control group of 90 age-sex matched healthy children (54.5%) [37]. It involves sustained liver damage and inflammation by inducing a strong immunological reaction in the liver that ultimately leads to cirrhosis and cancer after several decades of chronic infection. Although association with certain infectious agents is known, analysis of the presence of exogenous genomes in leukemia cells suggests that a single transforming agent is unlikely to cause leukemia development [11]. The mechanism for cancer development will probably involve several factors, wherein infectious agents can act as triggering factors. HL can be divided into two subtypes, EBV-associated and non-EBV-associated HL. Approximately 40 − 45% of the cases can be attributed to EBV infections, with high prevalence found in children under the age of 10 years. IL-6 and IFN-β levels were also increased following HSV-2 infection of HCE cells (Li et al., 2009).

Evidence of an associations of HL with EBV came from serological studies that showed elevated titers of anti-EBV antibodies in HL patients [39, 40]. In addition, the presence of viral DNA was demonstrated in malignant HL or Reed-Sternberg cells, where it established latency type II through the expression of Epstein-Barr nuclear antigen 1 (EBNA1), latent membrane protein 1 (LMP1), and latent membrane protein 2A (LMP2A) proteins [40, 41]. There are three clinical variant types of BL, endemic, sporadic, and HIV-associated types. The human tumor cell lines COLO-205, NCI-H226, and BT-549 as well as the normal primary cell line HEL were included in KRAS overexpression studies. The genome of KSHV has a 140.5-kbp coding region with at least 81 ORFs (54). HIV-associated BL patients are positive for EBV in one third of all cases [41, 42]. This finding suggests that BL is a polymicrobial disease [43], where malaria or HIV antigens act as co-agents in BL pathogenesis [44].

Although mucosa-associated lymphoid tissue (MALT) NHL occurs very rarely in children, it is noteworthy that its development is also associated with infection. The presence of H. pylori is demonstrated in almost all cases of MALT lymphoma [39, 40, 45]. Approximately half of the reported pediatric MALT lymphoma cases were observed in HIV positive patients [46, 47]. Eradication of H. Reliability was high for each of these tests (κ = 1.00 for HPV-16, HPV-18, and HHV-8 infections). Nervous system tumors occur frequently in children, especially CNS tumor that is the second most common pediatric cancer.

Infectious Agents and Cancer
There are many types of nervous system tumors, and they occur at different ages. Neuroblastoma can be diagnosed prenatally or during the first 3 months of life. More recently, at least eight new human polyomaviruses have been discovered (57), and one of these, MCV, was identified in patients with Merkel cell carcinoma (MCC), which is a rare but highly aggressive malignancy. v-Cyclin D transcripts detected by means of RT-PCR. Whether there is a genetic polymorphism which is crucial in a particular tumor type, or an involvement of toxins that regulate cell types at different stages of development remains unknown [50]. The very early onset of the disease suggests that parental factors may play a role during the period prior to conception, during gestation, or at birth [51]. DNA was digested with EcoRI and analyzed by Southern blotting, as described in Materials and Methods, with a probe consisting of the ORF74 coding region.

The infections linked to risk included rubella, mumps, varicella zoster, influenza, and herpes and respiratory infections [52, 53]. Polyomaviruses Simian virus 40 (SV40), John Cunningham virus (JCV), and BK are suspected to cause various oncological malignancies. These viruses were introduced into the human population in the 1950s [54] and SV40 was suspected to cause brain tumors [55]. Later retrospective studies found no correlation of SV40 contaminated vaccines with brain cancer [56, 57]. However, later reports found that the viruses were positively correlated with CNS tumors in adults and children [58, 59]. The presence of JCV in pediatric tumors was detected by immunohistochemistry, PCR, and Southern blot, using T antigen and agnoprotein markers, but different laboratories found a discrepancy in results [60]. In 62 cases of various pediatric CNS tumors (medulloblastoma, ependymoma, choroid plexus papilloma, and pilocytic astrocytoma) the viral DNA was found in 28% of the ependymomas, and in 20% of the choroid plexus papillomas [61].

In a 9-year-old patient diagnosed with pleomorphic xanthoastrocytoma, the genomic sequences of JCV LT, R, and VP1 were detected [62]. Further cases of JCV in pediatric pleomorphic xanthoastrocytoma were not reported. A member of polyomaviruses BK is implicated in nervous system carcinogenesis. The virus is expressed in neuroblastomas, but not in normal adrenal medulla, and it colocalizes and binds to p53 [33]. The carcinogenic mechanisms and properties of polyomaviruses (Table 1) identify them as at least acting as cofactors in carcinogenesis, especially in children who have immature immune systems. A growing number of studies on the herpes family of viruses and on childhood CNS tumors show positive correlations. Similar to EBV’s LMP-1, Tax strongly activates the NF-κB, AP-1 and CRE pathways that have a particularly potent pro-proliferative effect on lymphocytes, whereas Tax also interacts with several factors regulating chromatin remodeling, such as HDAC-1 and SWI/SNF, and causes the inhibition of DNA repair mechanisms, thus leading to genomic instability and ultimate transformation (Matsuoka and Jeang, 2007).

CMV DNA and proteins were detected in primary medulloblastoma, in cell lines, and in xenografts. Thirty-seven primary medulloblastoma cases were examined, and 34 (92%) expressed immediate-early proteins, and 27 (73%) expressed late viral proteins [63]. The virus and viral particles were also detected in glioblastoma multiforme (GBM), a rare tumor among children [64]. Many CMV viral proteins inhibit apoptosis in infected cells. At least six different proteins were associated with inhibition of apoptosis and could therefore enhance survival of CMV-infected tumor cells [27, 28]. It was reported that UL36 protein is responsible for chemotherapy resistance of infected cells in vitro [29]. CMV was also found to inhibit expression of HLA class I and class II antigens and antigen presentation, and thus activation of T-cells.

CMV can also inhibit NK cell activation and cytotoxicity [34]. At 2 days p.i., cells were fixed with methanol and stained by using Giemsa to visualize cytopathic effects (CPEs). Briefly, these are as follows: (i) the geographical distribution of viral infection should match that of cancer after adjustment for other cofactors. It is obvious that adult CNS tumors are different from childhood tumors. However, a scarcity of studies on the association of childhood nervous sytem tumors with infectious agents limits the understanding of the role of infectious agents. Therefore, studies of how and to what extent viruses, bacteria, and parasites can contribute to the development of childhood tumors are needed. There are many other types of benign and malignant tumors which occur rarely in children.

A case study of a child diagnosed with both sialoblastoma and hepatoblastoma demonstrated elevated levels of procalcitonin, proinflammatory stimulus to bacteria, and increased levels of C reactive protein, suggesting a response against bacterial infections [66]. Sialoblastoma affects parotid glands during infancy, and is rare, with only 24 cases reported in MedLine (1990–2008). Hepatoblastoma originates in the liver, and comprises less than 1% of reported tumors among children from infancy to 3 years of age [67]. trachomatis infection and prostate cancer. Hepatitis B virus (HBV) was found to be responsible for HCC in children in Taiwan, where HBV was endemic [69]. This relationship of HBV and childhood cancer was established as a result of discovering 100% HBsAg seropositivity among children with HCC and HBV DNA in their neoplasms [69, 70]. The role of HBV infection in the cause of hepatocellular carcinoma is further confirmed when Taiwanese HBV immunization programme significantly reduced the cancer incidence in vaccinated children compared to non-vaccinated children [71].

Clearly, much research into the epidemiology, virology, and molecular biology of a virus is needed before it can be accepted as an oncovirus. DNA was extracted from the following: 1) P3HR1, an Epstein- Barr virus-infected cell line; 2) Ram, an Epstein-Barr virusinfected lymphoblastoid cell line; 3) pleural effusion cells from a patient with acquired immunodeficiency syndrome-related Kaposi’s sarcoma who had pulmonary lesions; and 4) primary effusion lymphoma cells. It accounts for 5% of all childhood cancers [74]. Syrjanen et al. As shown in Fig. A direct oncogenic role of high risk HPV E6 and E7 proteins was identified. The viral proteins bind and thereby inactivate the tumor suppressors [32].

HPV probably employs the same mechanism of cancer development in different age groups, including children, and may act as an independent risk factor for oral cancer, another extremely rare childhood cancer [76]. To continue, nasopharyngeal carcinoma (NPC) is a rare cancer which occurs on the epithelium of the nasopharynx and accounts for about 1% of all childhood tumors. According to WHO there are three subtypes of NPC, including squamous cell carcinoma commonly found in adults, non-keratinizing carcinoma, and undifferentiated carcinoma. Childhood cancer cases are usually the latter subtype and EBV is involved in its aetiology [77, 78]. It was found that abundance of LMP1 expression of EBV protein correlated with a patient’s age. There were higher levels of LMP1 in younger patients’ specimens in Tunisia (n = 22 out of 82) [79]. It was in concordance with previous findings, where anti-viral capsid antigen, early antigen IgG and IgA levels were lower in juvenile form of NPC compared to adult form [80, 81].

NPC incidence is 1 per 100,000 children diagnosed annually in the US whilst it is more common in children of the Southeast Asia and Northern African region, with 8–25 per 100,000 cases recorded annually [82, 83]. In Hong Kong 80% of children are infected by 6 years of age and almost 100% have seroconverted by the age of 10 years [84]. The disclosure of the EBV nuclear antigen and viral DNA in the NPC demonstrated that EBV can infect epithelial cells and is associated with their malignant transformation. Kaposi’s sarcoma (KS) is a tumor, which originates from the cell lining of lymph or blood vessels. As such, LANA can cooperate with H-Ras to transform fibroblasts (Radkov et al., 2000). Classical KS is prevalent among elderly men; whilst younger generation, located close to African equator, is prone to endemic KS, or African KS. Epidemic KS occurs in patients with AIDS caused by HIV [85].

It is to be noted that before the onset of HIV in 1985 KS had been endemic in Africa [86]. It was reported that KS is caused by Human Herpes Virus 8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus) in children whose immune system is weakened [87, 88]. During the period of AIDS infection the cases of childhood KS increased more than 40-fold [89]. Prevalence of KS incidence among children is higher in Africa, where both HHV-8 and HIV are endemic, in contrast to well-resourced states, where patients have access to antiretroviral therapy [87, 90]. To sum up, the above-mentioned cancers are rare or even extremely rare in children, and more studies are needed to establish the mechanism of infection-based cancer development. However, there is still space to suspect the pathogens, which stimulate these rare malignancies in young generation. The mutation …

The other important protein in HPV carcinogenesis is E7, a phosphoprotein with two zinc fingers that shows some structural and functional similarity to adenovirus E1A and SV40 large T antigen. Various infections can also be acquired during passage through the birth canal if the mother is infected, or after admission to the nursery. It was also observed that HPV and EBV are sometimes found in breast milk and can be transmitted to the infant through breastfeeding [93]. Some of the above mentioned viruses are also found to cause tumors in adults (i.e., HPV in the cervix and in anogenital cancers, human HHV-8 in Kaposi’s sarcoma, and EBV in Burkitt’s lymphoma). Many mechanisms are used by infectious agents to survive in a host and create favorable conditions for neoplastic transformation. It is also possible that a child can inherit mutations that occurred in the germ cells of the parents via viral mutagenesis. Partial sequences of HHV-6A have been found in members of the same families [36].

All of the mechanisms listed in Table 1 could be exploited in combination, synergistically creating favorable conditions for neoplastic lesions to develop. Disruption of tumor suppression, in combination with apoptosis, immune evasion, and low-grade inflammation could enhance the accumulation of mutations, and this would select for preneoplastic cells, which over time could lead to the development of a tumor. Infants are born with an undeveloped immune system, and the prevalence of latent viral infections in adults that come in contact with newborns could facilitate the transmission of viruses. Thus, the chance of latent infections is likely. There are several proposed theories for childhood cancer development. Thus, the high-risk HPVs are powerful human cancer viruses that express oncoproteins that act at multiple stages in tumorigenesis from events involved in tumor initiation to later stages of tumor promotion. Therefore, this pattern of restricted HHV-8 gene expression in the majority of Kaposi’s sarcoma spindle cells provides additional support favoring a latent mode of HHV-8 infection in Kaposi’s sarcoma lesions.

It states that a child’s immature immune system requires early exposure to common infections for the proper immune system maturation. The lack of it leads to the aberrant response to infection. 3B, lane 4), or tissue from a normal mouse (Fig. they had aberrant response to delayed exposure to infectious agents [94]. Another hypothesis, the Kinlen hypothesis, proposes that a common infectious agent is responsible for increased leukemia cases transmitted by adults during a large-scale rural–urban population mixing [95]. Both Greaves and Kinlen hypothesis are supported by epidemiological data which accumulated over the past 15 years. They propose an unknown infectious agent (mostly viral by Kinlen) that trigger an aberrant immune response and thus can be a causative agent of childhood ALL.

A more recent unifying hypothesis, of “cell transformation by replication-defective mutants,” suggests that only viruses which have defects in replication machinery show elevated transformation potential, and when they are present in cells with certain chromosomal translocations, it can lead to leukemia development [96]. Finally, the “infective lymphoid recovery” hypothesis proposes that infective stress, triggering the heat shock response in infancy, stimulates proinflammatory cytokines and inhibits apoptosis. This, in turn, leads to a decline in antitumor immunity and in B-cell maturation arrest. This hypothesis addresses the infection paradox stated in Greaves’ and Kinlen’s hypotheses, that an unhygienic environment primes the adaptive immune response and is protective against childhood ALL, while multiple infections occurring later increase the risk of childhood ALL [97]. Overall, it is proposed that infection can be a triggering mechanism, and most likely, the immunological state, genetic alterations, and infections have a cumulative effect on leukemia development, and possibly on the development of other cancer types.

You may also like

Infectious Agents and Cancer

Infectious Agents and Cancer

This application is to establish the Malawi Cancer Consortium (MCC), aimed at developing capacity and conducting high-impact research focused on HIV-associated cancers in our setting. The aim of this study was to investigate the association between the infection by herpes simplex virus type 2 (HSV‑2) or human herpesvirus 8 (HHV‑8) and the risk of prostate cancer. The human herpes virus 8 (HHV8) and Epstein Barr Virus (EBV)-related cancers of Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) are most closely related to level of immune deficiency. My results demonstrate the presence of viral proteins in prostates from seropositive men and among tissues expressing these viral proteins, there is increased inflammation as measured by macrophage infiltrate. However, risk factors for KSHV infection, the exact mode of KSHV transmission and other epidemiological co-factors that may promote KSHV infection need further elucidation. In this study, KSHV seroprevalence in pregnant women attending antenatal clinics in the Gauteng province of South Africa was very high (45%) and nearly double that of HIV infection (23%). This means that you can’t change them.

Skin, for example, has an outer layer of epithelial tissue. The prevalence of KSHV slightly increased with increasing age among subjects in geographic areas where the prevalence of KSHV was high, such as Nigeria and Colombia, and it significantly decreased with increases in the educational level attained by subjects in those areas. Epstein-Barr virus infection and the pathogenesis of nasopharyngeal carcinoma: viral gene expression, tumour cell phenotype, and the role of the lymphoid stroma. None of these studies found any association between KSHV infection and other STD including syphilis. Since all the four polymorphisms play vital roles in the cell death pathway leading to altered mechanism of cellular apoptosis it is valuable to investigate the combined risks of CASP8 polymorphism with any (and all) of the FasR/FasL polymorphisms in cervical cancer, pre-cancerous lesions, HPV infection and HSV-2 infection. Higher antibody levels in HIV positive subjects may reflect poor immune control of KSHV resulting in more frequent reactivation. The lack of association between KSHV and age noted in this study may be attributed to the narrow age range studied (mean (± SD) 25.9 (6.2)).
Infectious Agents and Cancer

In this study, pregnant women with a higher level of education had lower rates of KSHV infection. The association between KSHV and increasing education has been shown in other studies [29]. Education is often reported to be a surrogate marker of socio-economic status. implying that those with lower socio-economic status are at a higher risk for KSHV infection, consistent with previous reports [18, 29]. We observed significant variation in the prevalence of KSHV between the regions within the Gauteng province of South Africa which remained after adjustment for several factors including age, HIV, syphilis status and education (Table 2). This is the first study in sub-Saharan Africa to demonstrate such geographical variation within a province. In the apartheid era, most South African townships were segregated according to ethnic and, therefore, geographic origin of the residents.

It follows that some of this variation may be explained by differences in cultural practices. People who have had another type of cancer have a higher risk of developing soft tissue sarcoma. In North America, nearly 13 out of 100, 000 men will be diagnosed with lip cancer during their lifetime. Therefore, we were unable to test this hypothesis. Infect Agent Cancer. Women attending routine ante-natal clinics are frequently used in surveys of HIV prevalence in South Africa and other African countries. Assessing KSHV prevalence in this population therefore allows for valid comparisons between this study and future studies in other parts of South Africa or other African countries.

This study adds to findings in South Africa and other African countries [31] which suggest a lack of evidence for sexual transmission of KSHV in heterosexual African populations. Cross-sectional studies of KSHV and other serology, while providing important information on risk factors for KSHV transmission, have limitations. A longitudinal study of KSHV transmission in South Africa is needed as well as studies aiming to identify geographical, cultural and/or lifestyle and environmental factors that may predispose people to KSHV infection.

You may also like

Infectious Agents and Cancer

Infectious Agents and Cancer

A staggering batch of over 30 papers published in Nature, Science, and other journals this month, firmly rejects the idea that, apart from the 1% of the human genome that codes for proteins, most of our DNA is “junk” that has accumulated over time like some evolutionary flotsam and jetsam.The papers, representing 10 years of work of the ENCODE (“Encyclopedia of DNA Elements”) project, completed by hundreds of scientists from dozens of labs around the world, reveal that 80% of the human genome serves some purpose and is biochemically active, for example, in regulating the expression of genes situated nearby. While baculoviruses normally infect insect cells, recombinant baculoviruses can serve as gene-transfer vehicles for transient expression of recombinant proteins in a wide range of mammalian cell types. A virus consists of genetic material, which may be either DNA or RNA, and is surrounded by a protein coat and, in some viruses, by a membranous envelope. Anyway, the majority of cancer-causing viruses integrate. 2006 Feb;12(1):65-71. Brains from GCV-treated and nontreated animals were examined immunohistochemically at different time intervals after grafting of CRIP-MFG-S-HSV-TK cells and GCV treatment. Two SFV miRNAs share sequence similarity and functionality with notable host miRNAs, the lymphoproliferative miRNA miR-155 and the innate immunity suppressor miR-132.

We therefore reviewed numerous studies in an attempt to determine whether certain viruses might be implicated in breast cancer, and we show association of this cancer with herpesvirus, polyomavirus, papillomavirus, and retrovirus. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. cassiquiarensis albigena subspecies is near threatened52,81 (). Reverse transcriptase is actually a combination of two enzymes: a polymerase that assembles the new DNA copy and an RNase that degrades the source RNA. EBV is classified as a class I carcinogen by IARC [5]. What seemed to intrigue clinicians and patients most about the 2009 study was that it involved a mouse virus that wasn’t thought to infect humans.

It is believed that the contradictions arise from the different methodologies used [13, 14]. In polymerase chain reaction (PCR)-based studies, positive correlation was shown [12], and the presence of EBV DNA was associated with more severe forms of breast cancer [15]. It includes the endogenous retroviruses. In a recent study, EBER-ISH results showed the presence of EBV in 47.5% of cases. Some envelope proteins facilitate viral entry into the cell, and others have directly pathogenic effects. This may suggest that causal association of the EBV and breast cancer might be due to changes in viral expression, resulting in changes in the tumour microenvironment. Viewed December 5, 2009.

Moreover, the mechanism of EBNA-1 action can be associated with the genetic polymorphisms of interferon-γ [16, 17]. Furthermore, the functions of the majority of viral miRNAs are unknown. HCMV has been shown to be involved in many cancers including malignant glioma, and prostate, skin, and colorectal cancers. Breast milk is one of the main routes of transmission of the virus, and breast epithelium may therefore be a major site of latent and active HCMV infection. When using immunohistochemistry to compare biopsy specimens from breast cancer patients versus controls, it was shown that HCMV infection may occur in breast epithelium of both normal and cancer patients. Photographs by Julio C Ruiz, DVM (Keeling Center for Comparative Medicine, MD Anderson Cancer Center). Cell-mediated immunity is essential, especially in dealing with infected host cells.

Analysis of IgG GM allotypes, which are associated with certain tumour antigens, showed that the most relevant non-self antigen in breast cancer patients was HCMV. It was speculated that the presence of a certain allotype and seropositivity for HCMV could have cumulative effects leading to breast cancer development [21]. However, CMV was not detected by recent RT-PCR analysis when investigating the prevalence of viruses in breast cancer tissue [22, 23]. There might be several mechanisms of how CMV can cause breast cancer initiation and progression. At this point, the individual had better hope that there is a competent immune system present to put down this “rebellion”. Secondly, HCMV exhibits immunosuppressive properties, leading to escape of tumour cells from immune surveillance mechanisms [24, 25]. Few viruses produce toxins, although viral infections of bacteria can cause previously innocuous bacteria to become much more pathogenic and toxic.

In a recent review [26] the role of IL-10 in breast cancer is discussed. Interestingly, both breast tumour inhibiting and promoting effects of the cytokine were shown. IL-10 was shown to be differentially expressed in breast tumour cells and infiltrating lymphocytes. The candidate miRNA sequences were synthesized in the context of minimal bacterial plasmids. The fact that HCMV expresses a viral analogue of human IL-10 may lead to the conclusion that this could be one of the mechanisms of breast cancer promotion by the virus. Members of the polyomavirus family, such as SV40, JCV, BK, and Merkel cell polyomavirus (MCPyV) have been associated with oncogenic diseases. Recently, 54 fresh frozen breast tumour samples were analyzed for the presence of 10 polyomaviruses [22].

2007. dengue virus a flavivirus, existing as four antigenically related but distinct types (designated 1, 2, 3, and 4), that causes both the classic and hemorrhagic forms of dengue. Interestingly, a related BK virus (BKV), in the same case study, gave negative results by direct sequencing [27]. Breast cancer samples were also negative for MCPyV [28]. Although, the presence of polyomaviruses within a tumour sample can show a link to tumour formation, it is important to identify viral mechanisms that lead to carcinogenesis. Below, we discuss results showing that polyomaviruses can directly cause cell immortalisation, hypermethylation of tumour suppressors, and spontaneous genetic alternations. Second, contrary to the genetic fundamentalism that currently informs medical thinking and public awareness, genes alone cannot possibly account for the complex psychological characteristics, the behaviors, health or illness of human beings.

SV40 virus was introduced into humans in the 1950s, when contaminated poliovirus vaccine was injected into millions of people. This has the most rapid onset of the hepatitis viruses affecting humans; transmission is easier than for the hepatitis B and C viruses, but infection generally does not persist. Such cancers contained SV40 DNA, which was mostly detected by PCR [30–32]. The SV40 presence was investigated by PCR which targeted Tag in 109 breast carcinomas, showing that SV40 DNA sequences were found in 22% of cancers. Immunohistochemical analyses confirmed the presence of virus in cancer cells. Ethidium bromide-stained low-molecular-weight (LMW) RNA is provided as a loading control. Mice and rat models showed that SV40 T/t-antigen expression in mammary epithelium results in pre-neoplastic lesions that progress to invasive and metastatic cancers [34, 35].

Infectious Agents and Cancer
Moreover, the immortalisation of normal human mammary epithelial cells can be achieved by SV40-induced transformation. SV40 large T-antigen contains an Rb-binding domain which causes altered gene expression and loss of p16(INK4a) expression [36]. Lastly, RASSF1A, SHP1, BRCA1, and TIMP3 methylation was higher in SV40-positive cases, with higher levels of P53 protein [37]. HIV-1 is found around the world and HIV-2 is found primarily in West Africa. JCV T-antigen binds and affects wild type p53, stabilizes b-catenin, and causes chromosomal instability. It activates ATM- and ATR-mediated G2 checkpoint pathways and causes G2 cell cycle arrest [38]. Expression of this protein also causes a metastatic phenotype in colorectal cancers [39].

HPV is a small DNA virus that is more often associated with cervical cancer in women. The information that your environment signals goes on to a regulatory protein, and only then does it go to the DNA which will end up coding a protein. HPV was also found in anogenital and oral carcinomas. HTLV-2 has been isolated from an atypical variant of hairy cell leukemia and from patients with other hematological disorders, but no clear association with disease has been established. HPV usually infects keratinocytes and mucous membranes. The virus is able to integrate itself into the host cell genome and use its transcription machinery to express viral proteins. Two of these proteins, early protein 6 and 7 (i.e., E6 and E7) inactivate tumour suppressor proteins p53 and pRb, respectively, and early protein 5 (E5) can affect receptor tyrosine kinases by associating with the cell membrane [41].

This analysis revealed readily detectable small RNAs corresponding mostly to the abundant products identified by small RNA sequencing. A recent control study summarised the results of molecular studies on the detection of high risk HPV in breast cancer samples and concluded that positive associations ranged from 0 to 86% [42]. The majority of molecular studies employed standard or nested PCR as methods of detection using commercially available primers for the L1 gene (codes for capsid protein). However, after obtaining positive results, primers for E6 and E7 genes, or for sequencing, reported possible sources of false positive and false negative results and limitation factors associated with detection methods used in those studies, such as confirmation of DNA/RNA quality, and adjustment for confounding factors [43]. Hernandez et al. respiratory syncytial virus (RSV) any of a genus of single-stranded paramyxoviruses; the name is derived from the type of disease produced (respiratory infection) and the microscopic appearance of the viruses in cell cultures. This might also be the case with advanced breast cancer samples.

It is also possible that the extent of HPV implicated in breast cancer is higher than studies have reported. Moreover, it has been reported recently that HPV is present in human breast milk [45], which indicates that the virus indeed can infect breast tissue and accumulate in it. Possible mechanisms of HPV in breast cancer carcinogenesis could be the same as in anogenital and head and neck tumours, via E6 and E7, or through a different pathway. Babies that were undernourished during pregnancy are more likely to be obese and experience metabolic problems later in life. Consistent with this possibility, Frega et al. RNA virus a virus whose genome consists of RNA. However, Dimri et al.

were able to immortalise human mammary epithelial cells in culture using E6 and E7 oncogenes [49]. Overexpression of c-MYC gene is a signature of the majority of breast cancers [50], and there is a significant association between elevated levels of c-Myc and HPV 16 infection. Noncanonical biogenesis of SFV miRNAs.We tested our original prediction of RNAP III-dependent transcription of the primary miRNA transcripts (pri-miRNA). E6 was not only found to elevate levels of c-Myc, but also was able to associate with the Myc complex and drive expression of its target genes. Moreover, c-Myc induces TERT (telomerase reverse transcriptase) transcription in the presence of E6 [52], which leads to increased telomerase activity, and hence immortalises HPV-infected cells. E7 was also found to elevate levels of c-Myc. This was observed in murine C127 cells infected with bovine papillomavirus type 1 [53] and in cells expressing HPV E7 [54, 55].

A virus consists of genetic material, which may be either DNA or RNA, and is surrounded by a protein coat and, in some viruses, by a membranous envelope. [56] were able to determine that E7 enhances c-Myc binding to the hTERT promoter, and suggested that E6 and E7 may work synergistically in order to induce transcription from the TERT promoter. There is also a possibility that latent viruses can be activated by sex hormones. Aceto et al. [57] detected HPV 16 in two cases of juvenile breast cancer after menarche, and one case of breast cancer after pregnancy and lactation. 3,000) encodes a protein. They were also able to detect E6 in peripheral blood samples from patients with stage IV juvenile breast cancer [57].

The possibility of this DNA fragment coming from latent urogenital infection was excluded because this was only the case in advanced cervical carcinoma. This is consistent with the finding that steroid hormones are able to bind to several regions in the control region of the HPV genome (LCR), enhancing expression of E6 and E7 of high-risk HPVs [58]. Investigators have tried to determine the involvement of HMTV in human breast cancers since 1943, when mouse mammary tumour virus (MMTV) was shown to cause mammary cancers in mice [59]. Several groups established that MMTV-like sequences were present in human breast cancer samples, but absent in normal tissues [60]. Ethidium bromide-stained low-molecular-weight RNA is provided as a loading control. In mice, the HMTV homolog promotes tumour formation through the insertion mutagenesis of Wnt oncogenes, thereby promoting its activation. In a recent study, Wnt-1 expression was higher in specimens which were positive for env, an envelope protein of MMTV, compared with env-negative specimens [61].

Env is typically absent in normal tissues and present in breast cancer tissues in both mice and human. In addition to the Wnt region, the common integration sites for MMTV were found to be in loci 35 that contain regions of the Fgf and Rspo gene families. The sites were frequently activated in tumours induced by MMTV, which primarily caused mammary premalignant hyperplastic outgrowth. Other genes were also deregulated, including Phf19 and Fox1. For example, Phf19 increased cell invasion capability and Fox1 promoted anchorage independent colony formation of MMTV infected cells. Approximately 20 of the HMTV common insertion site-associated genes are deregulated and/or mutated in human breast tumours [62]. HMTV sequences for env, gag, and sag from patients with ductal carcinoma and mammary hyperplasia have been cloned and sequenced, revealing the viral gene existence.

According to Dr. Moreover, the localisation of the MMTV env sequences to the nuclei of human breast cancer cells indicated that the provirus integrated into cancer cells [61]. These MMTV viral sequences were more common in conditions such as gestational [64] and familial breast cancers, indicating that a provirus could be transmitted or inherited. In addition, geographic localisation might also play a role in virus distribution. For example, the highest prevalence of viral sequence-positive breast cancer was in Tunisia, a Country known to have the highest prevalence of rapidly progressing inflammatory breast cancer in the world [65]. Inflammatory breast cancer is a form of breast cancer in which the presence of viral sequences are found to be associated with tumour aggressiveness in patients [66]. However, others produced an additional, slower-migrating band by Northern analysis that is consistent with the predicted longer primary transcript containing up to two pre-miRNA-like structures (Fig.

Cells infected with MMTV, like many other cancer cells, have highly active Src kinase. MMTV expressing cells escape apoptosis by activation of immune receptor tyrosine kinase-based activation motif-mediated Src tyrosine kinase signalling pathways [67]. EBV (68%), HPV (50%) and MMTV (78%) gene sequences are present and co-exist in many human breast cancers. Normal controls showed these viruses were also present in epithelial cells in human milk with less occurrence compared to breast cancer cells. The presence of these viruses in breast cancer is associated with younger age of diagnosis and possibly an increased grade of breast cancer [68]. These findings provide further evidence for a potential role of HMTV in breast cancer, but needs to be further investigated.

You may also like

Infectious Agents and Cancer

Infectious Agents and Cancer

Little is known about herpesviruses in Canadian pinnipeds. 10, no. Kaposi’s sarcoma-associated herpesvirus (KSHV) is a DNA virus that is linked to several human malignancies. We identified three novel GHVs, each present predominantly in one felid species: Felis catus GHV 1 (FcaGHV1) in domestic cats, Lynx rufus GHV 1 (LruGHV1) in bobcats, and Puma concolor GHV 1 (PcoGHV1) in pumas. In general, the characterized gammaherpesviruses exhibit a very narrow host tropism, which has severely limited studies on the human gammaherpesviruses EBV and Kaposi’s sarcoma–associated herpesvirus. This study is the first report identifying multiple viral proteins encoded by a human DNA virus that inhibit the cGAS-STING DNA sensing pathway. We hypothesized that bacterial end-products including short chain fatty acids (SCFA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) secreted by oral bacteria initiate viral reactivation from latency.
Infectious Agents and Cancer

Latently infected EBV, KSHV, and MHV 68 cell lines were incubated with crude spent media containing secreted SCFA, and components of bacterial pathogens (E. faecalis, Bacteriodes, Prevotella, Porphomonas, and Fusiobacterium Nucleatum). ElHV3 and ElHV4 form a distinct cluster, and ElHV5, ElHV6, TrHV1, and PrHV1 form a second cluster. Following incubation with crude spent media, viral immediate early promoters were activated, the viral early genes were upregulated as determined by RT PCR and western blot, and linear genomes were detected. HDAC inhibition activity as well as protein kinase C activity increased significantly following treatment with bacterial spent media. KSHV and EBV were consistently reactivated by bacterial metabolites but the mechanism of reactivation was both bacteria, virus, and cell type specific. Interestingly, EBV was preferentially reactivated following toll like receptor stimulation while KSHV and HSV-1 reactivation occurred following HDAC inhibition.

Secondly, we took functional proteomics approaches by establishing a genome-wide viral-viral and viral-host host-viral protein-protein interaction network through yeast-two-hybrid screening. However during viral reactivation, many of the chromatin modifications are changed resulting in the transcription and expression of many more viral genes.

You may also like

Infectious Agents and Cancer

Infectious Agents and Cancer

We have reported the case of a patient who presented with all the features of PEL that have been described elsewhere [14, 15]. Louis area has seen an alarming increase in new diagnoses of HIV and sexually transmitted infections among 13- to 24-year-olds. No one wants a std n like ur situation there r many people that have contracted them from broken trust, raped, etc not just from sleeping around. 3. its not curable. Development of persistent infection by NDV in normal cells, on the other hand, had also been well studied in normal cells [8–12], but not in cancer cells. There are data that shows nonoynol-9 may increase the risk of HIV transmission, However, the CDC recommends that latex condoms, with or without spermicides, should be used to help prevent sexual transmission of HIV.

Women with an HPV infection have an increased risk of developing cervical cancer. [9] Although KSHV seropositivity was not associated with HIV or HSV2 infections, with lifetime number of sexual partners, having at least one sexually transmitted disease were unrelated to KSHV seropositivity, it was inversely associated with ever use of condom use and positively associated with being married and with each additional child born, suggested a possible, albeit, small role of sexual transmission. Mol Psychiatry 2015; 20: 585593. HPV is a common sexually transmitted disease. This is especially true if they were overweight before pregnancy. The CDC recommends that latex condoms, with or without spermicides, be used to help prevent transmission of STDs. Many tests are done before the heart transplant.
Infectious Agents and Cancer

Try to avoid cutting or injuring yourself. Multiple marker screening is not diagnostic. You will likely need a full bladder for the test. For example, KS tumors in the lungs can cause breathing problems. Tell your doctor if you are sensitive to or are allergic to any medicine, latex, iodine, tape, or anesthesia. that KS patients attending the Uganda Cancer Institute were more likely to have a higher carriage of Strongyloides parasites than patients with other cancers treated at the same hospital [30] provide some support for the hypothesis. The hypothesis was also supported by a study of mother-infant pairs in Uganda [31], which reported that detection of malaria parasitaemia, hookworm and Mansonella perstans in stool was associated KSHV seropositivity.

Intriguingly, a causal link has been established for the roles of hepatitis B and hepatitis C in hepatic cancer (Alison et al., 2011), human papillomavirus virus (HPV) in cervical cancer (zur Hausen, 1996), Epstein Barr virus (EBV)—a herpes virus—in head and neck lymphomas (Burkitt, 1958), and HIV infections in an increased risk of non-Hodgkin lymphoma and Karposi’s sarcoma (Goedert, 2000). Sexually active women under age 26, older women at risk due to new or multiple partners, and men who have sex with men should have annual screening tests for chlamydia and gonorrhea. Exclusion of variables where prior studies indicated significant associations enabled us to confirm those previous associations after taking into account all available data. Make sure that you really love that person and plan to be with them for a long period of time. We are currently working to identify the receptor targeted on macrophages and to dissect the in vivo role of OMCP during cowpox infection. We also investigated the role of non-steroidal anti-inflammatory drugs (NSAIDS) in these relationships since regular NSAID use is associated with a modestly reduced risk of prostate cancer (Nelson and Harris, 2000; Jacobs et al., 2005). C-reactive protein (CRP) is a plasma protein that rises rapidly in the circulation in response to acute inflammation, infection, and tissue damage (Gabay and Kushner, 1999; Black et al., 2004).

This is the photo Guenther known as above — the first opt in her series. After my counseling, I had to wait some more before I could take my HIV test, and then have my blood drawn to test for everything else. Gonorrhea causes a discharge from the vagina or penis and painful or difficult urination.

You may also like