Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to computed tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the study were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment. Treatment was well tolerated, and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft-tissue sarcoma showed a reduction of >90% and >50% of the volume of two distant, noninjected metastases, lasting for 29+ and 26 months, respectively. Four other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude that repeated injections of < or =5 x 10(7) Vero-IL-2 cells are feasible and safe in heavily pretreated patients with advanced solid tumors. An additional evaluation of an intratumoral application of Vero-IL-2 seems warranted.
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PMID:Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors. 1035 13

Thirty-three metastatic melanoma patients were vaccinated according to a phase I-II study with an allogeneic melanoma cell line that was genetically modified by transfection with a plasmid containing the gene encoding human interleukin 2 (IL-2). The cell line expresses the major melanoma-associated antigens and the HLA class I alleles HLA-A1, -A2, -B8, and Cw7. All patients shared one or more HLA class I alleles with this cell line vaccine. Patients were immunized by three vaccinations, each consisting of 60 x 106 irradiated (100 Gy) melanoma cells (secreting 120 ng of IL-2/10(6) cells/24 hr) administered subcutaneously at weekly intervals for 3 consecutive weeks. Side effects of treatment consisted of swelling of locoregional lymph nodes and induration at the site of injection, i.e., a delayed-type hypersensitivity (DTH) reaction. In three patients, vaccination induced inflammatory responses in distant metastases containing necrosis or apoptosis along with T cell infiltration. Apoptosis occurred only in Bcl-2-negative areas, not in Bcl-2-expressing parts of the metastases. Two other patients experienced complete or partial regression of subcutaneous metastases. Seven patients had protracted stabilization (4 to >46 months) of soft tissue metastases, including one patient who developed vitiligo after vaccination. Immune responses to the vaccine could be detected in 67% of the 27 patients measured. Vaccination was shown to induce a variable change in the number of anti-vaccine cytotoxic T lymphocytes (CTLs) in peripheral blood, which did not correlate with response to treatment. However, in two of five patients the frequency of anti-autologous tumor CTLs measured was significantly higher than before vaccination. This study demonstrates the feasibility, safety, and therapeutic potential of vaccination of humans with allogeneic, gene-modified tumor cells, and that frequencies of vaccine-specific CTLs among patient lymphocytes can be determined by using a modified limited dilution analysis (LDA).
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PMID:Vaccination of melanoma patients with an allogeneic, genetically modified interleukin 2-producing melanoma cell line. 1075 53

Immunization to multiple defined tumor antigens for specific immune therapy of human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells. DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological effects were assessed by comparing response profiles using marginal likelihood scores. DC injections were well tolerated except for progressive vitiligo in two patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16 of 18 patients. An enhanced immune response to one or more MelAgs was seen in these same 16 patients, including 10 patients who responded to >2 MelAgs. The two patients failing to respond to both control and tumor antigens experienced rapid tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with immunity to two or less MelAgs had progressive disease 10 weeks after study entry, in contrast to tumor progression in only 1 of 10 patients with immunity to >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these patients. The overall immunity to MelAgs after DC vaccination is associated with clinical outcome (P = 0.015).
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PMID:Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. 1152 40

Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.
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PMID:Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma. 1643 52

The appearance of vitiligo-like lesions in patients with malignant melanoma is a well-known yet uncommon phenomenon. This finding is especially reported in patients undergoing immunotherapy with or without chemotherapy for malignant melanoma and is generally believed to be associated with a better prognosis. We report a case of preexisting vitiligo in a 48-year-old man, aggravated after chemo-immunotherapy of pulmonary metastatic melanoma with interferon-alpha, vinblastine and dacarbazine. Skin lesions remained stable after discontinuation of the treatment, and repigmentation heralded the recurrence of metastatic disease. These findings were in favor of vitiligo being a marker of the immunity against melanoma cells and its favorable impact on the prognosis of melanoma patients.
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PMID:The course of melanoma-associated vitiligo: report of a case. 1684 34

Different clinical studies report the connection between malignant melanoma (MM) and vitiligo, as the etiology of both diseases evolves around melanocytes. A case is presented of a 70-year-old female patient with metastatic MM in lymphatic node of the right groin, which developed simultaneously with the "vitiligo-like patches" over the face and extremities. Some authors suggest that the appearance of depigmentation during the course of MM might be considered a good prognostic sign. However, our patient subsequently developed multiple lung metastases as well as metastases in lymphatic nodes of the other groin region. This case shows that MM and vitiligo may develop simultaneously, indicating the possibility of similar mechanisms in the destruction of both benign and malignant melanocytes.
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PMID:Metastatic melanoma and vitiligo: a case report. 1685 16

Melanoma is a highly malignant tumor derived from skin melanocytes (pigment-producing cells), which is associated with a significant rate of systemic metastases and death. Various therapeutic approaches for melanoma have been attempted in recent years, including the use of chemotherapy, immunotherapy, and ablative surgical and radiation treatments. However, in many cases these treatments fail as the tumor becomes resistant to the treatment and rapidly spreads and causes death. Reports in the medical literature have documented the unique immunogenic nature of melanoma where antigens, antibodies, and immune complexes seem to play a major role in the course of the disease. Anti-melanoma antibodies can cross-react with antigens on normal melanocytes, therefore causing the appearance of an associated hypopigmentation that resembles vitiligo. Vitiligo is a dermatological disorder characterized by local, dispersed, or diffuse white patches on the skin as a result of the destruction of melanocytes. This disease is believed to be an autoimmune disorder since autoantibodies against membrane components of melanocytes are found in the sera of patients with vitiligo. Melanoma triggers an anti-tumor response in many patients. Unfortunately, such anti-tumor response is insufficient to elicit tumor regression and the tumor continues to proliferate. Since the prognosis of melanoma in patients and animals with vitiligo is more favorable than in the general population, it was hypothesized that sera from patients with vitiligo may react against melanoma cells. Such studies have demonstrated that exposure of tumor cells to the sera resulted in inhibition of proliferation of the melanoma cells in vitro and in regression of melanoma metastases in mice presumably on account of the presence of the high titer of anti-melanoma antibodies in the sera used in these studies. In this review we discuss the known data and hypothetical assumptions related to the use of vitiligo-associated antibodies against melanoma, as well as characterize the immune mechanisms involved in this process.
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PMID:Harnessing autoimmunity (vitiligo) to treat melanoma: a myth or reality? 1791 56

This unit details protocols for in vivo models of subcutaneous growth and pulmonary metastases of B16 melanoma. Therapeutic approaches include the use of B16.GM-CSF and rVVmTRP-1 to induce autoimmune vitiligo and tumor protection. The induction and use of gp 100-specific therapeutic cytotoxic T lymphocytes (CTL) are discussed. Methods are also included for CTL induction, isolation and testing, CTL maintenance, and adoptive transfer. Support protocols detail the testing of mouse sera for presence of MDA-specific antibodies by immunoblotting and ELISA, respectively. Additional sections, including growing B16 melanoma, enumerating pulmonary metastases, and use of recombinant viruses for vaccination, are discussed together with safety concerns.
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PMID:B16 as a mouse model for human melanoma. 1843 74

The association of vitiligo with immunologic therapy for melanoma is generally regarded as a good prognostic factor. Nevertheless, the immunopathogenesis of vitiligo remains incompletely understood. The authors report the case of a 71-year-old Caucasian woman who had a malignant melanoma on the posterior aspect of the left leg in 1982. The patient underwent wide local excision and elective left inguinal lymphadenectomy. Sixteen years later two amelanotic malignant melanoma metastases were observed on the left inferior limb and were excised. Interferon treatment was administered for only eight months owing to side effect intolerance. Two years later, vitiligo-like macules appeared over her face and trunk. Since then, several further cutaneous metastases were found; all of them were limited to the left inferior limb. The patient remained free of visceral metastasis until December 2007, when a single lung mass was identified on a CT scan. The distinctive feature in this patient was a long survival that was free of identifiable visceral metastases. Despite the two year gap between the appearance of vitiligo and interferon treatment, the former might be indicative of a delayed immunological response against the melanoma cells, supporting the concept of a better therapeutic outcome in this cluster of patients.
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PMID:Vitiligo: a good prognostic factor in melanoma? 1933 32

Vitiligo is an acquired depigmenting skin disease characterized by the loss of functioning epidermal melanocytes. Vitiligo can be associated with an autoimmune disorder. An unusual and important aspect of vitiligo is its relationship to melanoma. We present herein a 34-year-old man who developed regional lymph node metastases of malignant melanoma 2 years after the diagnosis of vitiligo.
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PMID:Do we have to pay more attention to vitiligo patients? Peculiar histopathological features of primary cutaneous melanoma preceded by vitiligo. 1987 96


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