Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/- 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.
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PMID:Interstitial hypertension in human breast and colorectal tumors. 142 83

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells results in significant tumor regression in patients with advanced cancer. We have investigated the kinetics of circulating erythroid (BFU-E) and granulocytic-macrophage (CFU-GM) progenitors after IL-2 therapy in 11 cancer patients, mainly affected by metastatic melanoma and renal cell carcinoma. Administration of IL-2 from day 1 through day 5 constantly induced a dramatic decrease of the number of circulating BFU-E and CFU-GM, which then showed a striking rebound (up to values fourfold and sevenfold higher, respectively, than the pretherapy levels) on discontinuation of IL-2, ie, from day 5 through day 10. A similar kinetic pattern was observed during and after the second cycle of IL-2 administration. 3[H]-thymidine killing experiments showed that the cycling activity of the progenitors was virtually unmodified in the rebound phases. To explore the mechanism(s) underlying this kinetic pattern, we have analyzed the plasma concentration of several hematopoietic growth factors, including IL-1 beta, IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and erythropoietin (Ep). No modifications in the levels of IL-3, GM-CSF, or IL-1 beta were observed, whereas a pronounced increase of IL-6 and G-CSF concentration was monitored, starting at day 3 and peaking at day 5 of treatment (a parallel, but modest, increase of Ep level was also observed). The elevation of IL-6 and G-CSF concentration is directly correlated with and may, at least in part, underlie the subsequent rebound of circulating hematopoietic progenitors. Furthermore, the increase in IL-4 level observed at day 10 of therapy may mediate the eosinophilia gradually starting at this stage of treatment.
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PMID:Adoptive immunotherapy with high-dose interleukin-2: kinetics of circulating progenitors correlate with interleukin-6, granulocyte colony-stimulating factor level. 170 62

We investigated the immunological properties of interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes (TIL), which were used for adoptive therapy of renal cell carcinoma (RCC) (seven patients) by focusing on natural killer (NK) cells, and metastatic melanoma (six patients) by focusing on cytotoxic T lymphocytes. TIL from five of seven cases proliferated well in culture with AIM-V serum-free medium and 1000 U/ml rIL-2 in 3-L gas permeable bags, whereas TIL from two RCCs exhibited delayed proliferation. Proliferation of CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted cytotoxicity in RCC-TIL (n = 6, mean = 651-fold, ranging from 39- to 3450-fold) for the first 2-4 weeks was 63 times higher than that of noncytotoxic CD3+ T cells (n = 6, 10.3-fold ranging from 0.8 to 35-fold). Thereafter, CD3+ T cells predominantly proliferated, and proliferation of CD3+ T cells (n = 5, 743-fold) for 5-6 weeks were 24 times higher than that of CD3-CD56+ NK cells (n = 5, 31-fold). Significant numbers of RCC-TIL became adherent to the surfaces of the bags several weeks after initiation of culture. These adherent TIL consisted of more CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-gamma, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ NK cells and, later, noncytotoxic CD3+ T cells proliferated in culture of RCC-TIL for adoptive therapy. These noncytotoxic TIL were primarily transferred to RCC patients, who also received cyclophosphamide, IL-2, and IFN-alpha. In contrast to RCC-TIL, IL-2-activated melanoma TIL consisting of all CD3+ T cells displayed modest levels of cytotoxicity, primarily restricted to autologous melanoma cells in all cases tested. The cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.
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PMID:Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC. 179 Jan 39

Adherent lymphokine-activated killer (A-LAK) cells, selected from peripheral blood lymphocytes (PBL) of normal human donors by adherence to plastic, and cultured in the presence of interleukin 2 (IL-2), are highly enriched in CD3-CD56+ natural killer (NK) cells. These IL-2-activated NK cells proliferate extensively upon further culture in conditioned medium containing IL-2. In contrast, we previously found that with PBL of some patients with advanced cancer, the same procedure often failed to yield high enrichment of NK cells or substantial expansion in the numbers of these effector cells. To obtain sufficient numbers of A-LAK cells for adoptive immunotherapy in cancer patients, an improved method for generation of human A-LAK cells with irradiated mitogen-stimulated allogeneic PBL- or Epstein-Barr virus-transformed lymphoblastoid cell lines was introduced. In paired experiments, A-LAK cultures with feeder cells showed significantly enhanced IL-2-driven proliferation of A-LAK cells obtained from normal donors or patients with metastatic melanoma, renal cell carcinoma, and other types of solid cancers. The growth-promoting effect of feeders for A-LAK cells resulted in significantly improved expansion of CD3-CD56+ (NK) effector cells in A-LAK cultures established from normal donors. Cells in these cultures also had significantly higher levels of antitumor cytotoxicity against K562 and Daudi targets than did A-LAK cells grown in the absence of feeder cells. Enrichment in CD3-CD56+ cells and antitumor activity also occurred in patient A-LAK cultures supplemented with mitogen-stimulated feeder cells, but was not statistically significant. Overall, despite improved proliferation and CD3-CD56+ cell content of A-LAK cultures established in the presence of mitogen-activated feeder cells, only 39% (21/54) of patients tested generated A-LAK cells that would be judged acceptable for large-scale therapeutic use by criteria based on fold expansion and purity of A-LAK cells. These results suggest that in comparison to normal individuals, NK cells of many patients with advanced solid tumors are defective in their ability to respond by proliferation to IL-2 even in the presence of exogenously supplied growth factors.
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PMID:Depressed ability of patients with melanoma or renal cell carcinoma to generate adherent lymphokine-activated killer cells. 179 Jan 41

Immunotherapy with tumor-infiltrating lymphocytes (TIL) activated in the presence of recombinant interleukin 2 (IL2) in vitro and adoptively transferred to patients with metastatic melanoma or renal cell carcinoma has resulted in complete or partial responses in some cases. These results have generated a wave of optimism and expectations, which may be premature. Much has been learned about TIL biology and their functional characteristics recently, but only few clinical trials have been completed to date. In this review, therapeutic potential of human TIL is evaluated based on limited knowledge of the antitumor mechanisms involved and imperfect understanding of events which occur during systemic administration of TIL. Limitations and advantages of TIL therapy are discussed and approaches to optimizing this form of therapy which are likely to be implemented in the future are summarized.
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PMID:Cancer therapy with tumor-infiltrating lymphocytes: evaluation of potential and limitations. 181 Apr 38

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.
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PMID:Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2. 183 84

The purpose of this study was to evaluate the efficacy and safety of a continuous-infusion interleukin 2 (IL-2) regimen for patients with metastatic melanoma and renal cell cancer. To investigate the contribution of adoptively transferred lymphokine-activated killer cells, patients were randomized to receive either IL-2 alone or IL-2 plus lymphokine-activated killer cells. Twenty-three patients with renal cell carcinoma and 20 with melanoma were entered into the protocol. There were no objective responses noted in the 38 assessable patients (20 with renal cell carcinoma, 18 with melanoma). Most patients demonstrated progressive disease following one 31-day cycle of weekly continuous-infusion IL-2. Grade I and II toxic reactions, including fever, rash, anorexia, and weight gain, were common and treated symptomatically. Significant in vivo stimulation of lymphokine-activated killer and natural killer cell activity was noted in most patients. This continuous-infusion IL-2 regimen with or without lymphokine-activated killer cells was ineffective in the treatment of melanoma and renal cell carcinoma.
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PMID:Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer. 185 52

Secondary tumors of the trachea are exceedingly rare, only 14 cases having been reported in the literature. Moreover, metastatic involvement of naso-paranasal cavities can be considered quite unusual. Approximately 150 cases have been drawn from the literature, most of which presented a metastatic deposit from a renal adenocarcinoma. Report is then made of a case of cutaneous melanoma metastatic to the trachea and nasal cavity. The tracheal lesion was repeatedly treated with Nd Yag laser, whereas no treatment was considered eligible for nasal metastasis. The patient succumbed to the tumor 16 months after diagnosis of tracheal involvement had been made. The tendency for malignant melanomas to metastasize to distant organs via the bloodstream is well known, yet trachea and nasoparanasal involvement by metastatic melanoma has been reported, respectively, in only three and six cases, including the present one. Prognosis is unfavorable due to the unusual coexistence of metastases to other organs and the lack of an adequate treatment.
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PMID:[Melanoma metastatic to the trachea and nasal cavity: description of a case and review of the literature]. 189 73

Chemotherapy does not only affect the viability of the tumor cell. It may also cause alterations in normal organs. Thus, tumor-free areas within human lung parenchyma of 63 surgical specimens of intrapulmonary metastases were analyzed to assess the extent of morphologic changes in response to previous cytostatic therapy. The material included 34 cases of sarcoma, 20 cases of germ cell tumors, 6 cases of hypernephroid carcinoma, two cases of mammary carcinoma and one case of metastatic melanoma. All patients had received cytostatic therapy in generally applied regimens for more than two years. Morphologic analysis was carried out by routine procedures. In addition to conventional staining procedures including HE, PAS, and Sirius stain, further tools were employed to extend the array of determined characteristics. To evaluate any changes in the tissue in order to specifically recognized carbohydrate structures, labeled neoglycoproteins or proteoglycans with specificity for endogenous receptors that bind to mannose, maltose, L-fucose, lactose, N-acetyl-D-glucosamine, and heparin were used. A monoclonal antibody binding the HLA-DR receptor was also included in the study. As a control, sections of 20 cases with intrapulmonary metastases without exposure to previous cytostatic therapy were included. To address the further question whether cytostatic therapy may induces changes in tumor-free lung that show similarities to the organ in question, sections from 18 cases with tuberculosis and from 37 cases suffering from sarcoidosis were similarly examined. Focal interstitial fibrosis was seen in 28/63 (44%) of the patients receiving chemotherapy. In contrast, only 2/20 (10%) patients of the untreated group exhibited this alteration. An active fibrosis with proliferating smooth muscle cells was found in two cases, dysplastic pneumocytes in 10 cases (16%) in the group with cytostatic therapy, but in no cases in the untreated group. Expression of the HLA-DR receptor in the pneumocytes was observed in 27/63 cases (43%) of the cytostatic cohort, in 21/37 (57%) patients of the sarcoidosis cohort, in 15/18 (83%) patients of the tuberculosis cohort, and in 1/20 (5%) of the untreated patients. In contrast to sections from treated patients, binding of neoglycoproteins was low in the untreated cohort. Interestingly, similarities between the tuberculosis cohort and the cytostatic cohort were seen for receptors that are specific for fucose and lactose, respectively. The results suggest that long-lasting cytostatic therapy induces focal fibrosis in 40%-50% of the patients, mainly via unspecific interstitial inflammatory infiltrates. A hypersensitivity reaction or direct toxicity may less frequently lead to pathologic alterations.
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PMID:Alterations in human lung parenchyma after cytostatic therapy. 200 Dec 78

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.
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PMID:Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study. 201 99


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