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

Signet ring lymphoma is a recently described morphologic variant of B cell lymphoma. We are reporting the first case of this subtype of follicular lymphoma that was initially confined to the skin and remained so. Light microscopy showed the tumor to be composed of monomorphous plump epithelioid cells with abundant eosinophilic cytoplasm involving the dermis and subcutaneous fat. Cytoplasmic vacuoles were present within some of the tumor cells, suggesting the diagnosis of adenocarcinoma with a signet ring appearance. Some of the vacuoles were positive on periodic acid-Schiff with diastase staining, and no mucin was identified. Immunostaining showed the presence of intracytoplasmic IgG heavy chains and kappa light chains. Characteristic intracytoplasmic inclusions, which were formed by saccules and microvesicular bodies, were seen by electron microscopy. The diagnosis of signet ring lymphoma was made. No systemic involvement was found. Over a period of 7 years, multiple new skin lesions occurred, all of which responded to radiation therapy. This rare variant of follicular center cell lymphoma, which can occur in the skin, should not be confused with metastatic mucinous adenocarcinoma and malignant melanoma.
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PMID:Signet ring lymphoma of the skin: ultrastructural and immunohistochemical features. 351 37

The immunogenicity of recombinant interleukin-2 (rIL-2, EuroCetus, Amsterdam, Netherlands) was studied in seventy-six patients receiving different subcutaneous immunotherapy regimens. Patients presented with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease. An enzyme immunoassay (EIA) was employed to screen patients for development of non-neutralizing antibodies against rIL-2, antibody specificity was confirmed by a standard Western blot. Neutralizing serum activity against rIL-2 was detected using a standard CTLL mouse proliferation assay. Additionally, serum levels of soluble interleukin-2 receptors and lymphocyte subsets expressing the CD56 natural killer (NK) associated antigen were measured. In a proportion of approximately 35% to 90% of the patients treated, non-neutralizing antibodies against rIL-2 could be detected after all treatment courses were evaluated. Antibodies were of the IgG, IgM, IgA and IgD subtypes. None of the 76 patients exhibited serum neutralizing activity after one treatment course. Five patients exhibited neutralizing anti-rIL-2 serum activity after two or more treatment courses of systemic rIL-2. In three of these patients, antibodies neutralized both recombinant and natural IL-2. Patients developing neutralizing anti-rIL-2 antibodies, exhibited significantly lower serum sIL-2 receptor levels upon the emergence of serum neutralizing activity than patients without antibody. Additionally, NK cell associated CD56 positivity was significantly lower in patients who exhibited neutralizing anti-rIL-2 serum activity than in patients who did not. A significant decrease in levels of soluble IL-2 receptors and CD56 NK cell positivity was observed, when comparing values prior to and after onset of serum neutralizing activity against rIL-2. However, while emergence of neutralizing antibodies to rIL-2 diminished rIL-2 induced biological activation, it did not coincide with abrogation of treatment response.
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PMID:Immunogenicity of recombinant human interleukin-2: biological features and clinical relevance. 751 68

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-alpha, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-alpha at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-alpha was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreatment using rIL-2, rIL-2 and rIFN-alpha, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific to rIL-2.
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PMID:Low-dose interleukin-2 in combination with interferon-alpha effectively modulates biological response in vivo. 768 66

An 80-year-old white female developed clinical signs of a large choroidal malignant melanoma in her left eye. There were no signs of metastatic disease, but an asymptomatic chronic lymphatic leukemia was discovered. Histopathologic examination of the enucleated left eye showed a mostly necrotic malignant melanoma of the choroid with areas of spindle B cell differentiation, episcleral extension and secondary angle-closure glaucoma with necrosis of the anterior segment of the eye. On the basis of immunocytochemical studies of the lymphocytic infiltrates in the iridal blood vessels, retinal blood vessels and the choroid, the leukemic disease was classified as B cell lymphoma of low malignancy (lymphoplasmacytoid immunocytoma). A reactive T lymphocytic infiltration of the conjunctival stroma was also noted. Patients with malignant melanomas of the uvea require exclusion of a second malignancy.
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PMID:Necrotic malignant melanoma of the choroid and concurrent intraocular manifestation of malignant non-Hodgkin's B cell lymphoma. 818 27

A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin-activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin.
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PMID:A wide range of human cancers express interleukin 4 (IL4) receptors that can be targeted with chimeric toxin composed of IL4 and Pseudomonas exotoxin. 831 73

Bryostatin 1 is a naturally occurring macrocyclic lactone which when applied to cells in culture activates protein kinase C (PKC). In vivo bryostatin 1 functions as an anticancer agent with activity against murine lymphomas, leukemias, and melanoma. Because all organs and tissues contain PKC, normal cells would also be a likely target for this agent. Here we demonstrate that in vivo administration of bryostatin 1 activates platelets over a dose range of 0.4 to 40 micrograms/kg with half-maximal activation occurring at 3 micrograms/kg and stimulation of neutrophils over a similar dose range. This in vivo activation of neutrophils is associated with a rapid decrease in measurable cytosolic PKC, a finding consistent with translocation of the enzyme to the membrane. In contrast, no statistically significant change in PKC location was found in liver, spleen, brain, or L10A B-cell lymphoma. However, in culture the L10A lymphoma did respond to bryostatin 1 with translocation of PKC. To evaluate whether the lack of effect of bryostatin 1 on PKC in organs was secondary to rapid degradation, we developed a bioassay to measure the levels of bryostatin 1 in the blood. To measure the presence of bryostatin 1, human neutrophils were incubated with plasma from mice given injections of different concentrations of bryostatin 1. Using this assay, bryostatin 1 at levels as low as 60 nM could be measured in the plasma. A time course with this bioassay demonstrated that less than 10% of the bryostatin 1 injected was detectable after 2.5 min. These results demonstrate that bryostatin 1 is capable of activating platelets and neutrophils and modulating PKC in vivo. The lack of effect of bryostatin 1 on specific organs may be secondary to the rapid clearance/degradation of this compound from the blood.
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PMID:In vivo administration of the anticancer agent bryostatin 1 activates platelets and neutrophils and modulates protein kinase C activity. 850 23

The expression of intercellular adhesion molecule 1 (ICAM-1), a molecule pivotal in many inflammatory and immune paracrine interactions, has been highly correlated with malignant melanoma (MM) progression. Because numerous parallels exist between tissues of neural crest origin and the immune system in the regulation of postmitotic cell survival, ICAM-1 expression was studied in MM and compared with that of B-cell lymphoma/leukemia 2 protein (bcl-2 oncoprotein), an important regulator in prolonging lymphoid cell survival by blocking programmed cell death. Frozen sections from 33 cases were studied by immunoperoxidase techniques: 14 primary MM (five in situ), nine metastatic MM (one epidermotropic), four melanocytic nevi, and six normal skin controls. The percentages of the cells that stained and their intensities (0-4+) were graded. Both ICAM-1 (90%, 3-4+) and bcl-2 (95%, 2-4+) were strongly expressed in all nine metastases, including the epidermotropic disease extension. Bcl-2 strongly decorated the tumor cells in all 14 cases of primary MM (80%, 2-4+); in the five in situ MM, bcl-2 stained the atypical melanocytes at the dermal-epidermal junction (DEJ) and throughout the epidermis (75%, 1-2+). In contrast, ICAM-1 was negative in the in situ MM. ICAM-1 expression became strong (85%, 2-4+) in the dermal component of early invasive disease. Both ICAM-1 and bcl-2 were expressed in melanocytic nevi, decreasing in intensity deep within the dermis as the nevus cells senesced ("matured"). Only bcl-2 was expressed in the normal melanocytes of the six skin controls. These data show that bcl-2 is constitutively expressed in normal melanocytes and melanocytic nevi and persists in the transformed cells of early and late MM. ICAM-1 is expressed only after dermal involvement occurs, both in melanocytic nevi and in invasive MM; it persists in metastatic disease. The coexpression of bcl-2 and ICAM-1 demonstrates another similarity between the immune and neural crest systems, but it does not define or necessarily imply any functional interaction between the two proteins. The intercellular relationship of these two molecules, if any, remains to be investigated.
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PMID:Intercellular adhesion molecule 1 (ICAM-1) and bcl-2 are differentially expressed in early evolving malignant melanoma. 859 46

Thirty-one seminars have been held in the 16 years since 1981. A principal interest from the beginning was the genetics of cancer, well before this subject became widely popular. This interest arose in part because of marked binational differences in type-specific cancer rates, such as the very low rates among Japanese for Hodgkin's disease in the young, testicular cancer, Ewing's sarcoma, superficial spreading melanoma, chronic lymphocytic leukemia, and Wilms' tumor (half the U.S. frequency). Three seminars were devoted to the seeming reciprocal relationship between B-cell lymphoma (low in Japan) and certain autoimmune diseases (high in Japan), which is perhaps similar in origin to the male/female differences in the rates for these diseases. A seminar on Li-Fraumeni syndrome led to the recognition of cases among Japanese pedigrees brought to the meeting, and generated a study of its occurrence in Japanese families with adrenocortical carcinoma in a child. Another seminar revealed a marked clustering of rare cancers in Werner's (premature aging) syndrome in Japan, and led to a binational study and analysis of case-reports worldwide. Three seminars on pathology heightened appreciation of the importance of subclassifying cancer by subsite and subtype for racial and other comparisons. Four seminars on biostatistics in cancer research generated a substantial exchange of specialists and trainees in this field.
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PMID:The U.S.-Japan Cooperative Cancer Research Program: some highlights of seminars, interdisciplinary program area, 1981-1996. 861 22

Secondary cutaneous neoplasia, e.g. basal cell malignant carcinomas or squamous cell carcinomas, is frequently observed in patients with malignant lymphomas. The association between malignant lymphoma and secondary malignant melanoma has only been rarely reported. We describe a patient with a low-grade nodal B-cell lymphoma who, while on treatment with steroids and an alkylating agent, developed a malignant melanoma level IV which rapidly metastasized to lymph nodes involved by the malignant lymphoma.
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PMID:[Metastatic malignant melanoma in treated non-Hodgkin's lymphoma]. 899 30

Intranasal administration of 10(4) U of murine interferon (IFN)-alpha/beta prolonged the survival time of DBA/2 mice injected i.v. with 10(5) (> 20,000 LD50) IFN-alpha/beta-resistant 3C18 Friend leukemia cells (FLC). Long-term survivors rejected a second challenge with 3C18 FLC without additional IFN-alpha/beta treatment. IFN-alpha/beta administered intranasally was not effective in 3C18 FLC-challenged DBA/2 mice pretreated with antibody to IFN-alpha/beta. Recombinant human IFN-alpha BDBB, which is cross-reactive on mouse cells, also increased the survival time of 3C18 FLC-challenged DBA/2 mice. Placing 10(4) U IFN-alpha/beta twice a day into the nostrils also prolonged the survival time of DBA/2 mice with 3-day established 3C18 FLC tumors. Administration of 10(4) U IFN-alpha/beta into the nasopharynx was equally effective or more effective than an equivalent amount of IFN-alpha/beta given by the i.p or oral routes or by gavage. Intranasally administered IFN-alpha/beta also increased the survival time of C57B1/6 mice challenged i.v. with EL4 T cell lymphoma cells, DBA/2 mice challenged i.v. with L1210R B cell lymphoma cells, and C57B1/6 (H-2b) and DBA/2 (H-2d) mice challenged i.v. with B16 melanoma cells (H-2b). These results may be important in devising novel therapeutic strategies for malignant disease using type I IFN.
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PMID:Intranasal administration of IFN-alpha/beta inhibits the development of visceral tumor metastases. 904 69


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