Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Burkitt's lymphoma is the most common childhood cancer in Africa. Most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. When first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. Subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. Today, Burkitt's lymphoma is considered an example of multistep carcinogenesis. Each step in the process results from a different agent. The agent in the first step is the Epstein-Barr virus, which infects B cells of the immune system causing a proliferation of these cells. The second step, malarial infection, furthers the proliferation of B cells providing a large population of cells available for a chromosomal translocation which represents the third step in the formation of the lymphoma. The chromosomal translocation places a cancer causing gene, c-myc, in close proximity to an active antibody-encoding its proliferation resulting in a cell capable of unlimited growth which serves as the nucleus of a B cell lymphoma.
 ...
PMID:Burkitt's lymphoma and the role of Epstein-Barr virus. 216 60

Physicians who think epidemiologically are rare. A method is suggested for detecting their aptitude early in their career when help may be offered to make the most of their special talent. Clusters geographically or in families may provide clues to cancer etiology. Clusters have been systematically thought by mapping cancer mortality in the US and independently in China. Case-control studies have revealed environmental exposure responsible for some of the clusters. Clusters noted by alert clinicians or other astute observers have revealed most of the known environmental causes of human cancers. Genetic influence in carcinogenesis has been identified by studies of peculiar cancer occurrence, such as familial aggregation, multiple primary cancer or the occurrence of cancer with other diseases as, for example, congenital malformations and immunodeficiency disorders. Ethnic differences in cancer occurrence may be revealing. Thus, in Japan there is low frequency of B-cell lymphoma but high frequency of certain autoimmune diseases, as if inherent protection against one predisposes the other. As a rule of thumb, the occurrence of three rare observations is not likely to be due to chance. Examples include ideal carcinoma in three persons with cystic fibrosis of the pancreas who survived to about 30 years of age, and the occurrence in Klinefelter's syndrome of germ cell tumor of the pineal--a neoplasm that has an unusually high frequency in Japan. Finally, the history of discoveries concerning cancer etiology, an aspect of what Comroe has called "research on research", can point the way to new discoveries in the future.
 ...
PMID:Nakahara memorial lecture. Rare events and cancer epidemiology. 333 98

The immune system has evolved under Darwinian pressures as a defence against ubiquitous viruses. Immune surveillance against viral antigens protects the normal host. Individuals with inherited or acquired immune-deficiency disorders can become vulnerable to ubiquitous viruses and neoplasms can ensue, such as B-cell lymphoma, hepatocellular carcinoma, squamous-cell carcinoma, Kaposi's sarcoma, and carcinoma of the penis and uterine cervix. Immunodeficiency permits Epstein-Barr virus, hepatitis B virus, papillomavirus, herpes simplex virus, and cytomegalovirus to induce sustained target-cell proliferation. Each virus selects specific cellular targets bearing viral receptors and the infection leads to proliferation of the target cells rather than lysis. Various co-factors, including nutrition, exposure to tumour-promoting agents, parasitic infection, and ultraviolet light, may promote carcinogenesis. Depending on the type and severity of the immune deficiency, gradual proliferation may lead to evolution of a malignant clone. Conversion of polyclonal virally infected proliferating cells to give monoclonal malignancy is probably due to specific cytogenetic rearrangements which allow oncogene activation and endow an altered tumour cell with selective growth advantages over normal diploid cells. Prevention of viral oncogenesis may be possible by treatment of immune-deficient individuals with premalignant disorders. Immunotherapy and antiviral therapy may prevent progression of viral-induced proliferation to malignancy. The purpose of this paper is to discuss and evaluate the role of immune deficiency and viruses in the induction of malignancies commonly occurring in Africans residing in sub-Saharan Africa (Purtilo, 1976). The types of malignancies commonly occurring in this region are believed to be due to ubiquitous viruses. A failure of immune surveillance mechanisms to recognize viral antigens and abrogate proliferation of infected target cells predisposes to malignancy by increasing the chance of a proliferating cell undergoing a cytogenetic or molecular alteration which endows it with malignant characteristics. The immunological surveillance hypothesis has been elaborated during this century by Ehrlich, Thomas, Burnet, and Schwartz (reviewed by Purtilo & Linder, 1983). This hypothesis rests on several assumptions: that neoplastic cells possess unique tumour antigens: tumour antigens provoke an immune response in the host; and the immune response is protective and eliminates the tumour.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Squamous-cell carcinoma, Kaposi's sarcoma and Burkitt's lymphoma are consequences of impaired immune surveillance of ubiquitous viruses in acquired immune deficiency syndrome, allograft recipients and tropical African patients. 610 Feb 88

When a patient with non-Hodgkin's lymphoma (NHL) undergoes a relapse, immunological testing of malignant lymphocytes usually shows that the relapse cells are derived from the original tumor clone. We have observed a patient with a B cell lymphoma whose cells bore surface membrane IgG kappa at diagnosis and IgG lambda at clinical relapse 21 months later, during which time he had received multiple-drug chemotherapy. The shift from kappa to lambda light chain expression implies that the patient's apparent relapse was in fact due to the development of a second tumour. This may be another example of cytotoxic drug-induced carcinogenesis in a patient with a lymphoproliferative disorder.
 ...
PMID:A case of IgG lambda lymphoma occurring in a patient with previous IgG kappa lymphoma. 679 57

Viruses implicated in the development of human cancers include hepatitis B (and C) viruses in hepatocellular carcinoma; human papillomaviruses in anogenital cancers; Epstein-Barr virus in nasopharyngeal carcinoma and Burkitt's lymphoma; human T-cell leukaemia/lymphoma viruses in adult T-cell leukaemia/lymphoma; and indirectly, human immunodeficiency viruses in Kaposi's sarcoma and B-cell lymphoma. Together, they contribute significantly to the cancer statistics in the Southeast Asian region. Neoplastic proliferation may be instigated by the presence and expression of viral oncogenes which may be integrated into the host genome and/or exist in episomal molecules. Critical viral genes may also interfere with host genes, resulting in the activation of cellular proto-oncogenes and/or the inactivation of anti-oncogenes and their products. The molecular pathogenesis of virally-induced cancers has led to major breakthroughs in the understanding of carcinogenesis at a molecular level. The occurrence of some of these viruses in a significant proportion of normal individuals suggests long latency periods necessitating multi-step co-operating events arising from multi-factorial agents such as host genetic susceptibility, immunological and hormonal status, as well as chemical and physical cocarcinogens in the environment. Successful intervention achieved with effective vaccines such as the hepatitis B vaccine and measures to severe the chain of viral transmission culminating in reduced incidence of the corresponding cancer will provide conclusive evidence for the virus-cancer relationship.
 ...
PMID:Cancer and viruses. 810 16

Mutations in the N-, K-, and H-ras genes are key events in the process of carcinogenesis of many human cancers and may serve as important targets for therapeutic intervention. We developed a simple diagnostic method that in one step and within 5 hr determines the mutational status of any of the 3 ras genes in a given tumor sample. The method combines polymerase chain reaction (PCR) with denaturing gradient gel electrophoresis (DGGE) and allows simultaneous mutation scanning of 6 regions covering "hot-spot" codons 12, 13 and 61 of the 3 ras genes. The sensitivity of the assay was demonstrated by the analysis of control mutations, either naturally occurring or created by site-directed mutagenesis. We further demonstrate that unambiguous identification of ras mutations can be achieved by heteroduplex analysis in denaturing gradient gels, circumventing sequence analysis. We applied the method to establish the mutational status of all 3 ras genes in 123 samples of B-cell non-Hodgkin's lymphoma. Altogether, one diffuse large B-cell lymphoma and one B-cell chronic lymphocytic leukemia (B-CLL) harbored a mutation (G12S and G12A, respectively) in the K-ras gene, and one B-CLL harbored a mutation (Q61R) in the N-ras gene. We therefore conclude that ras mutations only contribute rarely, if at all, to carcinogenesis in B-cell non-Hodgkin's lymphoma.
 ...
PMID:A one-step DGGE scanning method for detection of mutations in the K-, N-, and H-ras oncogenes: mutations at codons 12, 13 and 61 are rare in B-cell non-Hodgkin's lymphoma. 913 69

In order to investigate specific DNA damage caused by nitric oxide (NO) induced lipid peroxidation, levels of promutagenic etheno adducts 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) were measured in spleen DNA of SJL mice induced to produce high levels of NO by injection of RcsX (pre-B-cell lymphoma) cells. epsilondA and epsilondC levels were quantified by an ultrasensitive immunoaffinity-32P-post-labeling method. Spleen DNA of control mice (n = 5) had background levels of 9.2+/-5.4 epsilondA adducts per 10(9) dA and 13.1+/-5.7 epsilondC adducts per 10(9) dC. In RcsX cell-injected mice (n = 7), levels of these adducts were elevated approximately 6-fold, i.e. 53.9+/-39.4 epsilondA per 10(9) dA and 83.5+/-57.8 epsilondC per 10(9) dC (P < 0.05). Mice injected with RcsX cells and also treated with NG-methyl-L-arginine (NMA), an inhibitor of inducible nitric oxide synthase (n = 6), had significantly reduced levels (P < 0.05) of both epsilondA and epsilondC (13.5+/-5.7 epsilondA per 10(9) dA and 28.2+/-15.7 epsilondC per 10(9) dC). These findings constitute the first available evidence of formation of etheno adducts associated with NO overproduction in vivo. The adducts were presumably formed from lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE), generated via oxidation of lipids by peroxynitrite. The results suggest that etheno-DNA adducts, among other types of damage, may contribute to the etiology of cancers associated with chronic infection/inflammation in which NO is overproduced.
Carcinogenesis 1998 Dec
PMID:Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide. 988 60

The RCK gene is a target of the t(11;14)(q23;q32) chromosomal translocation observed in human B-cell lymphoma, and the overexpression of its protein (rck/p54) by the translocation was shown to cause malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. The expression of rck p54 in colorectal adenocarcinoma cells was examined by immunohistochemistry and Western blot analysis. The rck/p54 protein was found to be overexpressed in tumour tissues resected from 13 (50%) out of 26 cases of colorectal adenocarcinomas and two out of two (100%) cases of colonic severe dysplastic adenomas. In view of activities of rck/p54 determined in other tissue types, we suggest that rck/p54 may contribute to the cell proliferation and carcinogenesis at the translational level in the development of colorectal tumours.
 ...
PMID:Overexpression of rck/p54, a DEAD box protein, in human colorectal tumours. 1036 Jun 75

Specific defects in DNA repair pathways are reflected by DNA microsatellite instability (MSI) and play an important role in carcinogenesis. Reported frequencies in gastric non-Hodgkin's lymphomas (NHL) vary from 14% to as high as 90%. Another form of genetic instability in tumours is allelic imbalance (AI) due to loss or gain of genetic material at a specific chromosomal region. This might point to the presence of a tumour suppressor gene or oncogene. We examined both MSI and AI in 26 gastric lymphomas (10 low-grade and 13 high-grade MALT lymphomas and three cases lacking MALT features and categorised as diffuse large B cell lymphoma (DLCL)). Tumour components and normal cells (epithelium, muscle) were microdissected from paraffin-embedded resection samples. Contrary to other studies we did not observe frequent MSI when investigating 18 different loci distributed over 12 chromosomes. Microsatellite instability of a single locus was found in 1/10 (10%) low-grade MALT lymphomas and 2/13 (15%) high-grade MALT lymphomas. These data indicate that DNA mismatch repair genes do not play a role in the pathogenesis of these lymphomas. Allelic imbalance was detected in 60% (6/10) of low-grade MALT lymphomas, in 62% (8/13) of high-grade MALT lymphoma and in 67% (2/3) of DLCL. In high-grade lymphomas more loci showed AI (one to seven loci, with a mean of 2.5 loci per case) than in the low-grade lymphomas (one to two loci, with a mean of 1.3 loci per case), possibly reflecting an increased genomic instability.
 ...
PMID:Frequent allelic imbalance but infrequent microsatellite instability in gastric lymphoma. 1055 55

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.
 ...
PMID:Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia. 1060 21


1 2 3 4 5 6 7 8 9 10 Next >>