Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 19-year-old woman presented with a large mediastinal mass, histologically shown to be malignant lymphoma of lymphoblastic type (LBL). Immunophenotypic and gene rearrangement analysis unequivocally demonstrated that the neoplasm was of B-cell lineage. The neoplastic cells expressed terminal deoxynucleotidyl transferase, the pan-B cell antigens CD19, CD20, and CD22, and were negative for immunoglobulins and numerous T-cell antigens tested. Southern blot analysis showed rearrangement of one allele of the immunoglobulin heavy chain gene while the immunoglobulin kappa and T-cell receptor beta chain genes were in the germline configuration. Thus, the immunophenotypic and molecular findings in this case correspond to an early stage of B-cell differentiation, the pre-pre B-cell stage as has been named by others. In contrast with LBL of immature T-cell lineage, precursor B-cell LBLs involving the mediastinum are truly rare. Occasional cases have been reported that have arisen elsewhere and subsequently involved the mediastinum at time of relapse or tumor progression. Well-documented examples of immature B-cell LBL arising in the mediastinum are virtually unreported. The site and cell population giving rise to this neoplasm is unknown. However, origin from precursors of normal thymic medullary B cells is proposed as one possibility.
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PMID:Mediastinal lymphoblastic lymphoma with an immature B-cell immunophenotype. 131 99

Seventeen patients with refractory follicular lymphoma heavily treated with chemotherapy (>2 regimens), radiotherapy, and biological modifiers were enrolled in a pilot study to receive six weekly doses, instead of the more frequent four doses, of monoclonal anti CD20, at a standard dose of 375 mg/m(2). In an intent-to-treat analysis, overall response was 76%, of which 47% (8 patients) were a complete response. With a median follow-up of 33.6 months, 7 complete responders remained alive and free of disease, and 2 partial-response patients remained stable without additional treatment. Actuarial curves showed that at 3 years, 53% of patients should be alive and free of disease. The 4 patients who were failures died secondary to tumor progression. Overall survival at 3 years was 76%. Toxicity was mild; all patients completed the schedule on time and doses. The addition of two doses of anti-CD 20 clearly improved the outcome in a group of patients with refractory follicular lymphoma heavily treated and poor prognostic factors. However, the number is too small to drawn definitive conclusions, and more clinical trials are necessary to determine if four of six doses of anti-CD20 therapy are better in this setting of patients.
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PMID:Rituximab in the treatment of refractory follicular lymphoma -- six doses are better than four. 1135 79

We describe a case of testicular B cell lymphoma with deletion of chromosome 5, del(5)(p11), as a sole structural abnormality. Histopathological diagnosis of the tumor was a high-grade lymphoma of the diffuse type containing cells positive for B cell specific antigen (CD20) and negative for the leukocyte common antigen (CD45). Deletion 5p may define the region of a tumor suppressor gene that could be associated with tumor progression and invasiveness and may serve as an indicator of poor prognosis in testicular lymphomas.
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PMID:Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma. 1173 24

The treatment of primary central nervous system lymphoma (PCNSL) with chemo- and radiotherapy is efficient in terms of tumor response. However, time to tumor progression often is of short duration and leptomeningeal relapse is common. We present a 66-year-old man in third relapse of a CD20-positive PCNSL. After treatment with intravenous and intraventricular administration of the chimeric anti-CD20 monoclonal antibody rituximab, a total clearing of lymphoma cells in the cerebrospinal fluid (CSF) was achieved. There was no change in the size of the parenchymal tumor mass but there was slight improvement of clinical symptoms after therapy. Rituximab infusions (375 mg/m2) were first given systemically on days 1 and 8. Intraventricular injections of rituximab via Ommaya reservoir were given on days 16 (10 mg), 17 (40 mg), 24 (25 mg) and 25 (25 mg). Reversible side effects such as nausea, chills and hypotension were observed only immediately after intraventricular administration of 40 mg rituximab. Antibody levels in CSF were measured at 7 timepoints during and after the treatment period. These data suggest that intraventicular treatment with rituximab is safe and feasible with a potential activity on leptomeningeal tumor manifestation. Efficacy and pharmacokinetics of rituximab in PCNSL should be investigated in future trials.
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PMID:Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximab. 1224 Nov 17

Treatment with radio- and chemotherapy has become increasingly efficient in primary CNS lymphoma (PCNSL). However, time to tumor progression is often short, and the majority of patients eventually relapse. Therefore, new therapeutic modalities are needed. One possible new option is the use of monoclonal antibodies (moabs) such as the humanized anti-CD20 moab rituximab. Treatment with intravenous rituximab has resulted in response rates of 50% in systemic non-Hodgkin's lymphoma and was also efficient in PCNSL as well as in CNS involvement of systemic disease. However, rituximab concentrations in the cerebrospinal fluid are low after systemic application. Therefore, the authors performed an intraventricular rituximab treatment in 2 patients. The most recent results and the possible role of moabs in patients with PCNSL are summarized and discussed.
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PMID:Treatment of CNS lymphoma with the anti-CD20 antibody rituximab: experience with two cases and review of the literature. 1297 2

The anti-CD20 monoclonal antibody rituximab induces remission in 40% to 60% of patients with indolent B-cell lymphoma, but virtually all patients have relapses. We evaluated the efficacy of concurrent administration of another biologic agent, N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) with rituximab against a variety of human B-cell lymphoma cell lines (Ramos, DHL-4, and FL-18) in vivo. Concurrent 4HPR and rituximab administration prevented tumor progression of lymphoma-bearing mice in a minimal disease model (rituximab + 4HPR, 100% progression free; rituximab alone, 37.5% progression free, P =.01; 4HPR alone, 12.5% progression free, P <.01; controls, 0% progression free, P <.01). Combinations of 4HPR + rituximab exceeded the predicted 50% additive rate of disease control from each agent alone (P =.038). Administering 4HPR and rituximab to mice with established tumors induced complete responses (CRs) in 80% of animals compared with 20% to 40% CRs using either agent alone (P =.07), resulting in significantly improved survival. Tumors harvested from 4HPR + rituximab-treated mice displayed elevated caspase activation compared with untreated controls (P =.02). Adding a broad-spectrum caspase inhibitor in vivo fully abrogated the antitumor effects of 4HPR + rituximab (P =.05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies.
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PMID:Fenretinide enhances rituximab-induced cytotoxicity against B-cell lymphoma xenografts through a caspase-dependent mechanism. 1469 37

Recent advances in molecular biology have led to the development of selective molecular targeting agents for genes involved in cell proliferation, apoptosis, and angiogenesis in cancer cells. The current success of molecular targeting therapy is shown by: imatinib mesylate (STI571, Gleevec), targeted to the Bcr/Abl fusion protein derived from a translocation between chromosomes 9 and 22 in chronic myelogenous leukemia; rituximab (Rituxan), a monoclonal antibody to CD20 used in non-Hodgkin's lymphoma; trastuzumab (Herceptin), a chimeric monoclonal antibody to HER-2 used in breast cancer; and gefinitib (ZD1839, Irresa), a tyrosine kinase inhibitor of the epidermal growth factor receptor used in non-small cell lung cancer. The superior therapeutic efficacy of these molecular targeting agents over traditional chemotherapy has been shown by the survival benefit achieved for patients with advanced or recurrent cancers. Although the precise molecular mechanisms by which these agents produce or enhance an antitumor effect, alone or in combination with anticancer drugs, are not known, the specific inhibition of target genes critically involved in tumor progression and metastasis by the agent is clear. However, further studies to determine which patient groups and anticancer drugs are appropriate for combination therapy with these molecular targeting agents are needed. Herein, we discuss the current status and potential for overcoming drug resistance in solid tumors and focus on the differential features of the tumor microenvironment in solid and hematologic malignancies.
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PMID:Changes in therapy for solid tumors: potential for overcoming drug resistance in vivo with molecular targeting agents. 1505 42

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.
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PMID:Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma. 1719 84

Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carcinoma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of "tumor budding", a feature which can be highly specific for tumors showing an infiltrating tumor growth pattern. Importantly, tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact, several tumor-associated antigens such as CD3, CD4, CD8, CD20, Granzyme B, FOXP3 and other immunological or inflammatory cell types have been identified as potentially prognostic in patients with this disease. Evidence seems to suggest that the balance between pro-tumor (including budding and infiltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand, the infiltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other, the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features, such as the BRE and Gleason scores, the ratio of pro- and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease.
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PMID:Invasive front of colorectal cancer: dynamic interface of pro-/anti-tumor factors. 2001 53

Tumor-infiltrating lymphocytes (TILs) in gastric adenocarcinoma show a strong compartmentalization with high numbers of lymphocytes in the stroma and low intraepithelial lymphocyte counts. Our previous study has shown stromal regulatory T cells (Treg) to be associated with a beneficial outcome in intestinal type cancer of the cardia. We undertook the present study to further evaluate the immunogenic and inflammatory environment in intestinal-type gastric adenocarcinoma of the cardia. We assessed CXCR3 expression, Epstein-Barr virus (EBV) status, Her2/ERBB2 status and overexpression/amplification using tissue microarrays (immunohistochemistry and in situ hybridization) of 52 patients. The data were correlated to different TIL subset counts (CD3, CD8, GranzymeB, FoxP3 and CD20) and to infiltrating histiocytes (CD68) both in the tumor and the surrounding stromal tissue that were reported earlier. Her2/ERBB2 overexpression/amplification showed no correlation to tumor stage. Moreover, for the first time, we show here that Her2/ERBB2 overexpression/amplification has no correlation to overall or subset-specific TIL infiltration. EBV infection was seen in four cases and showed a strong association with intratumoral CD8(+) T cell infiltration as well as a moderate correlation to stromal CD8(+) T cell accumulation. Intratumoral CD8(+) T cell infiltration was significantly correlated to intratumoral FoxP3(+) Treg infiltration, and to a lesser extent, to stromal FoxP3(+) Treg counts. Stromal CXCR3(+) T cell infiltration showed an inverse correlation to T category. This highlights the importance of stromal immune processes for cancer growth and suggests a subversion of Th1 immunoresponse in cancer progression and underlines the important role of inflammation for early carcinogenesis.
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PMID:Inflammation in gastric adenocarcinoma of the cardia: how do EBV infection, Her2 amplification and cancer progression influence tumor-infiltrating lymphocytes? 2135 45


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