Background: Desmoid tumor, also known as aggressive fibromatosis, is a rare soft tissue tumor. For those cases localized in the anterior abdominal wall, radical resection and reconstruction with a mesh is indicated. Because the rarity of the disease, randomized trials are lacking, but in reported retrospective series, it is clear that although it is considered a benign lesion, local recurrence is not uncommon.
View Article and Find Full Text PDFBackground: Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with relapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta.
Methods: Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse.
Background: Although widely used for the management of patients with cutaneous melanoma, the sentinel lymph node (SLN) biopsy (SNB) procedure raises several issues. This study was designed to investigate: the predictive factors of SLN status, the false-negative (FN) rate, and patients' prognosis after SNB.
Patients And Methods: This is an observational, prospective study conducted on a large series of consecutive patients (n = 1,313) enrolled by 23 Italian centers from 2000 through 2002.
We explored in a phase I/II clinical trial the combination of valproic acid (VPA), a clinically available histone deacetylase inhibitor, with standard chemoimmunotherapy in patients with advanced melanoma, to evaluate its clinical activity, to correlate the clinical response with the biological activity of VPA and to assess toxicity. Patients were treated initially with VPA alone for 6 weeks. The inhibition of the target in non-tumour peripheral blood cells (taken as a potential surrogate marker) was measured periodically, and valproate dosing adjusted with the attempt to reach a measurable inhibition.
View Article and Find Full Text PDFUnlabelled: Several epidemiological, pre-clinical and clinical studies support Vitamin D as a preventive and therapeutic cancer agent.
Background: Vitamin D and cancer: calcitriol, the biologically active form of vitamin D (1,25(OH)D), exerts its effects mainly through binding to nuclear vitamin D receptor (VDR). Calcitriol has been shown to be an anti-proliferative, pro-differentiation, pro-apoptotic agent and an inhibitor of cell migration.
Predisposition to familial cutaneous malignant melanoma has been associated with mutations in the CDKN2A and CDK4 genes. However, only a small subgroup of melanoma pedigrees harbour CDKN2A or CDK4 germline mutations. It is possible that other types of CDKN2A rearrangements, not detectable by routine PCR-based approaches, are involved in a fraction of melanoma cases negative for point sequence changes.
View Article and Find Full Text PDFThe aim of this study was to determine whether excision biopsy and primary closure of primary cutaneous melanoma modifies lymphatic drainage and accuracy of sentinel node biopsy. Thirty patients with 31 cutaneous melanomas were prospectively enrolled to undergo lymphoscintigraphy (LS) before and after excision biopsy. Tc-human serum albumin nanocolloid was first injected intradermally around the primary tumor and subsequently, after excision biopsy, adjacent to the scar.
View Article and Find Full Text PDFA comprehensive bibliographic search of the literature was conducted to identify studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer (NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D serum levels. Fully adjusted risk estimates were found and extracted for the two polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in the meta-analysis, with a total of 6805 skin cancer cases.
View Article and Find Full Text PDFHeat-shock proteins (HSPs) are a group of proteins whose expression is increased when the cells are exposed to elevated temperatures or other stressful conditions. This increase in expression is transcriptionally regulated. The function of HSPs is similar in virtually all living organisms, from bacteria to humans.
View Article and Find Full Text PDFBackground: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability.
Methods: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years.
Recent Pat Anticancer Drug Discov
June 2008
Use of monoclonal anti-CTLA4 antibodies represents a new promising strategy to block the activation of immunosuppressive CTLA-4 and thus induce tumour regression. This review is mainly focused on the report of existing data on the clinical use of Ipilimumab (formerly MDX-010) in the treatment of metastatic melanoma. Several phase I and II trials have been conducted to evaluate safety and efficacy of this form of immunotherapy either alone or in combination with vaccines or chemotherapy in patients with stage III or stage IV melanoma.
View Article and Find Full Text PDFPurpose: To assess the antitumor activity of vitespen (autologous, tumor- derived heat shock protein gp96 peptide complexes) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician's choice.
Patients And Methods: Patients (N = 322) were randomly assigned 2:1 to receive vitespen or physician's choice (PC) of a treatment containing one or more of the following: dacarbazine, temozolomide, interleukin-2, or complete tumor resection. This open-label trial was conducted at 71 centers worldwide.
Numerous individuals and institutions throughout the world have contributed to the development of hematopoietic stem cell transplantation (HSCT) for autoimmune diseases. In this review, we will summarize what we have learned at our own institution (Northwestern University), and how it has guided our therapy. An emphasis will be placed on both the scientific basis for the development of autologous hematopoietic stem cell transplantation and a summary of the data in a variety of human diseases.
View Article and Find Full Text PDFInterferon-alpha-2b (IFNalpha2b) is the only effective adjuvant therapy for melanoma patients at high risk of recurrence that has been approved by regulatory authorities worldwide. However, IFN toxicities increase the risk of poor treatment compliance and impair the potential for benefit from this agent. A review of the literature demonstrated little recent attention to supportive care in the management of IFN toxicities.
View Article and Find Full Text PDFBackground: Despite the high survival rates reported for screening-detected cases, the potential of screening of high-risk subjects for reducing lung cancer mortality is still unproven. We herewith present the baseline results of a randomized trial comparing screening for lung cancer with annual spiral computed tomography (CT) versus a yearly clinical review.
Methods: Male subjects, 60-74 years old, and smokers of 20+ pack-years were enrolled.
Methylation of tumor suppressor genes is among the most frequent alterations in patients with malignant pleural mesothelioma (MPM). The aim of this study was to analyze the promoter methylation status of four tumor suppressor genes, p15(INK4B), p16(INK4A), RASSF1A and NORE1A in MPM. Samples of 79 MPM patients were analyzed using a methylation-specific PCR method.
View Article and Find Full Text PDFBackground: The early detection of lymph node metastases may have important prognostic and therapeutic implications in melanoma patients. The purpose of this study was to investigate whether specific clinical and/or dermoscopic features could be "in vivo" predictors of sentinel lymph node (SLN) positivity in melanomas >1 mm thick.
Materials And Methods: Five Italian centres (Istituto Dermopatico dell'Immacolata, IDI, Rome; Skin Cancer Unit, Oncologia Dermatologica, CPO, Ravenna; Istituto Europeo Oncologico, Milan; Centro di Riferimento Oncologico, Aviano; Istituto Nazionale Tumori, Naples) carried out a blind retrospective study on 508 melanomas observed from January 1994 to December 2002.
Interdigitating and follicular dendritic cell sarcoma (DCS) are very rare diseases, with approximately 184 cases being reported thus far, and their best treatment modality is still on debate. This is a review of all the cases of dendritic cell sarcoma reported from 1981 until April 2006. This review is enriched with the original contribution of five cases occurred at our Institution from 1994 to 2006.
View Article and Find Full Text PDFBone Marrow Transplant
September 2007
Autologous hematopoietic stem cell transplantation (HSCT) utilizing a myeloablative regimen containing total body irradiation has been performed in patients with systemic sclerosis (SSc), but with substantial toxicity. We, therefore, conducted a phase I non-myeloablative autologous HSCT study in 10 patients with SSc and poor prognostic features. PBSC were mobilized with CY and G-CSF.
View Article and Find Full Text PDFPurpose: In a previous immunohistochemical study of dendritic cells (DC) in sentinel lymph nodes (SLN) draining regressing melanomas, we found that the accumulation of mature DC-LAMP(+) DCs in SLNs was associated with local expansion of antigen-specific memory effector CTLs and the absence of metastasis in downstream lymph nodes. The aim of this study was to investigate the prognostic importance of the maximal density of mature DCs in SLNs.
Experimental Design: A total of 458 consecutive patients with micrometastatic melanoma within SLNs were eligible for analysis.
It is widely held that cells with metastatic properties such as invasiveness and expression of matrix metalloproteinases arise through the stepwise accumulation of genetic lesions arising from genetic instability and "clonal evolution." By contrast, we show here that in melanomas invasiveness can be regulated epigenetically by the microphthalmia-associated transcription factor, Mitf, via regulation of the DIAPH1 gene encoding the diaphanous-related formin Dia1 that promotes actin polymerization and coordinates the actin cytoskeleton and microtubule networks at the cell periphery. Low Mitf levels lead to down-regulation of Dia1, reorganization of the actin cytoskeleton, and increased ROCK-dependent invasiveness, whereas increased Mitf expression leads to decreased invasiveness.
View Article and Find Full Text PDFCutaneous melanoma is a "perfid", aggressive and hard to be treated malignant tumor in case of delayed diagnosis. However, patients still have a chance to escape progressive disease if the lesion is recognized early, when the surgical approach is curative. Dermoscopy has the important advantage of rapidity and non-invasivity in a field with (still) contradictory algorithms of diagnosis and treatment.
View Article and Find Full Text PDFIn non small cell lung cancer (NSCLC) patients undergoing surgery after induction chemotherapy, all mediastinal lymphnodes potentially involved by tumor should be resected whenever possible. Paratracheal bilateral lymphadenectomy for left sided tumors can be disabling, i.e.
View Article and Find Full Text PDFRibonucleic acid (RNA) has been shown to have a key role in the maintenance of normal cellular function and host resistance to infection. The effect of experimental diets containing RNA on microbial translocation, killing of translocated bacteria and the survival rate of the host was studied in a burn animal model which included immunosuppression. Balb/c mice were fed for 10 days with an RNA supplemented diet (AIN/76A).
View Article and Find Full Text PDFBackground: Bronchopleural fistula following lung resection is a therapeutic challenge for thoracic surgeons.
Case Presentation: We describe a case of late bronchopleural fistula after right extrapleural pneumonectomy for malignant mesothelioma. Bronchoscopic attempts to repair it were unsuccessful.