[Peripheral T-cell lymphoma: diagnosis and treatment].
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Humans↗
Biomedical subjects
R Dummer
Publications and source records attributed to R Dummer.
Melanoma cultures show different susceptibility towards E1A-, E1B-19 kDa- and fiber-modified replication-competent adenoviruses.
Replicating adenovirus (Ad) vectors with tumour tissue specificity hold great promise for treatment of cancer. We have recently constructed a conditionally replicating Ad5 AdDeltaEP-TETP inducing tumour regression in a xenograft mouse model. For further improvement of this vector, we introduced four genetic modifications and analysed the viral cytotoxicity in a large panel of melanoma cell lines and patient-derived melanoma cells. (1) The antiapoptotic gene E1B-19 kDa (Delta19 mutant) was deleted increasing the cytolytic activity in 18 of 21 melanoma cells. (2) Introduction of the E1A 122-129 deletion (Delta24 mutant), suggested to attenuate viral replication in cell cycle-arrested cells, did not abrogate this activity and increased the cytolytic activity in two of 21 melanoma cells. (3) We inserted an RGD sequence into the fiber to extend viral tropism to alphav integrin-expressing cells, and (4) swapped the fiber with the Ad35 fiber (F35) enhancing the tropism to malignant melanoma cells expressing CD46. The RGD-fiber modification strongly increased cytolysis in all of the 11 CAR-low melanoma cells. The F35 fiber-chimeric vector boosted the cytotoxicity in nine of 11 cells. Our results show that rational engineering additively enhances the cytolytic potential of Ad vectors, a prerequisite for the development of patient-customized viral therapies.
Adenoviridae↗
Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion.
Bexarotene is an oral retinoid therapy that is effective for the treatment of early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have failed on other therapies. However, bexarotene treatment is associated with unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism, which are manageable with adequate concomitant medications and are reversible on cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated hypertriglyceridaemia and hypothyroidism is suggested, based on data from the studies with bexarotene in CTCL and on day-to-day experience with this agent in the clinical setting. The strategy anticipates that these common adverse events are likely to occur and recommends the early use of preventive therapy to lower triglycerides and elevate thyroid hormone levels in the blood, followed by subsequent monitoring, dose adjustment during bexarotene treatment, and titration of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most patients. When further information becomes available on how bexarotene interacts with lipid metabolism and thyroid function, the management approach suggested here may need to be changed.
Anticarcinogenic Agents↗
HLA-G expression in basal cell carcinomas of the skin recurring after radiotherapy.
Basal cell carcinoma (BCC) of the skin represents the most common malignancy in the fair-skinned population worldwide. HLA-G is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in recurring BCCs, we constructed a tissue microarray containing 38 primary BCCs that underwent radiotherapy and 14 secondary BCCs recurring on the primary site after radiotherapy, and evaluated the HLA-G protein expression by immunohistochemistry. The HLA-G protein was most frequently expressed in aggressive sclerosing BCCs. Nodular BCC demonstrated the strongest HLA-G expression. Interestingly, tumor infiltrating mononuclear cells (TIMC) expressed the HLA-G molecule in BCCs that showed no recurrence. After comparing primary BCCs and BCCs relapsed after radiotherapy, we observed decreased HLA-G expression on tumor cells and the loss of HLA-G expression on TIMC in relapsed BCCs. After radiotherapy, immunobiology of BCC may change resulting in the down-regulation of HLA-G expression on tumor and on tumor-infiltrating cells.
Basal Cell Carcinoma↗
Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma.
Melanoma is the most common lethal cutaneous neoplasm. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated in 2001. These have been approved by all Swiss medical societies involved in the care of melanoma patients. New data necessitated changes concerning the safety margins (reduction to maximally 2 cm) and modifications of the recommendations of follow-up.
Combined Modality Therapy↗
Atypical poorly differentiated cutaneous T-cell lymphoma with an angiocentric growth pattern presenting histologically as vasculitis.
We report the case of a 41-year-old patient with an aggressive cutaneous T-cell lymphoma (CTCL) initially presenting on histology as lymphocytic vasculitis. On repeated histological examination and by molecular biology work-up, the diagnosis of an unclassifiable CTCL could eventually be established. This atypical poorly differentiated lymphoma was of a CD4+ CD8- CD56- phenotype and followed an unfavourable course. The patient died despite chemo- and immunotherapy 7 months after the first consideration of lymphoma as diagnosis.
Adult↗
[Cutaneous lymphoma].
Cutaneous lymphomas are uncommon. They must be distinguished from secondary skin manifestations of primary nodal lymphomas. Primary cutaneous lymphomas are divided into B-cell- and T-cell cutaneous lymphoma and commonly have good prognosis. Therapy is based on the stage of the disease. Since cure is not possible, the aim of treatment is to control the disease and reduce symptoms. A variety of new and promising therapeutic modalities have been introduced in recent years.
Antineoplastic Agents↗
Baseline staging in cutaneous malignant melanoma.
BACKGROUND: Baseline staging in patients with primary cutaneous malignant melanoma (MM) is routine, but the diagnostic accuracy and the impact on clinical outcome are still unclear. OBJECTIVES: To evaluate the sensitivity and specificity of baseline staging in the early detection of regional lymph node metastases or distant metastases in patients with MM. METHODS: One hundred consecutive patients with MM of Breslow's tumour thickness over 1.0 mm were enrolled. All patients had an extensive baseline staging including physical examination, ultrasound (US) of the abdomen and regional lymph nodes, chest X-ray, whole-body positron emission tomography (PET) and sentinel lymph node biopsy. The sensitivity and specificity of detection of macroscopic or microscopic metastases in the regional lymph nodes or at distant sites were calculated for each method. RESULTS: Sentinel lymph node biopsy was positive in 26 patients. US detected two of 26 histologically tumour-positive sentinel nodes (sensitivity 8%, specificity 88%) and PET two of 26 (sensitivity 8%; specificity 100%). There were three lymph node metastases with a diameter > 4 mm. All of them were found suspect at physical examination. Two of them were detectable with US, two with PET, and all were identified with either US or PET. Nine patients had suspect findings at distant sites, which were all false positive on further investigation (specificity of the combined staging procedures 91%). At 18 (6-37) months' follow-up, five of 26 (19%) patients with a positive sentinel node and four of 74 (5%) of patients with a negative sentinel node had recurrent or progressive disease. CONCLUSIONS: The combination of physical examination and lymph node US detects the great majority of patients with macroscopic lymph node metastasis (approximately 3% of patients at baseline). Only 10% of patients who have a histologically tumour-positive sentinel node are macroscopically detectable. Altogether, approximately 25% of patients have a positive sentinel node biopsy, among 90% microscopic. The value of whole body staging at baseline remains limited, since distant metastases can hardly ever be detected. The survival benefit of baseline staging and surveillance in patients with cutaneous MM remains to be established by comparative prospective trials.
Abdomen↗
SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphoma.
BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative disorder of mainly CD4+ T cells, with primary manifestation in the skin. OBJECTIVES: To detect new CTCL-associated antigens for immunological therapies and to define their specificity in terms of RNA expression and seroreactivity. METHODS: A newly constructed CTCL cDNA phage library was screened and cross-reactivities against the detected clones were tested using 15 mycosis fungoides and six Sézary syndrome sera. The mRNA expression of the identified genes was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using 22 tumour tissues, nine cell lines and up to 29 different types of normal tissue. RESULTS: We identified nine different tumour antigens (HD-CL-01 to HD-CL-09) of which seven clones had high homology to genes with known functions. Several of these genes had previously been associated with cancer, namely inositol 1,4,5-triphosphate 5-phosphatase, vimentin, aldose reductase and elongation factor-1alpha. Variations in the deduced protein sequences were observed in three cases, mostly due to variations in protein length. The individual clones were recognized by up to 56% of patients' sera, while control sera were negative except in one case. Using RT-PCR, we found a frequent expression of these new tumour antigens in tumour specimens (26-100%). In contrast to humoral specificity, specific mRNA was also detected in selected normal tissues (29-89%). CONCLUSIONS: SEREX (serological identification of antigens by recombinant expression cloning) identified multiple tumour-associated antigens in CTCL. The serological specificity and the high percentage of reactive sera of CTCL patients against several clones suggest these genes as potential targets for diagnostic and prognostic purposes.
Antigens, Neoplasm↗
Efficacy of laser treatment of tattoos using lasers emitting wavelengths of 532 nm, 755 nm and 1064 nm.
BACKGROUND: Multifunctional laser devices can be used to treat tattoos successfully. OBJECTIVES: To report the efficacy of laser treatment in professional, amateur, accidental and permanent make-up tattoos from our own experience and to compare it with the literature. METHODS: We retrospectively studied 74 consecutive patients with professional, amateur, make-up and accidental tattoos between June 1998 and November 2000. Patients were treated with a Q-switched Nd:YAG laser (wavelengths of 532 nm and 1064 nm), a Q-switched alexandrite laser (755 nm) and a variable pulse Nd:YAG laser (532 nm). RESULTS: Fourteen patients (19%) achieved a complete response (>95% lightening of treated tattoos), 23 (31%) an excellent response (76-95% lightening) and 21 (28%) a good response (51-75% lightening). Sixteen patients (22%) showed only a slight improvement (< or =50% lightening). Make-up tattoos and blue-black professional tattoos were most successfully treated. Multicoloured professional tattoos needed more treatments (mean +/- SD 5.7 +/- 5.4) in comparison with single-colour tattoos (3.5 +/- 2.0). The amateur tattoos needed fewer treatments (2.8 +/- 1.1) in comparison with professional tattoos. With accidental tattoos the results depended on the particles which had penetrated the skin. In contrast to literature reports, newer tattoos showed a trend to better treatment results than older tattoos. CONCLUSIONS: Using modern Q-switched lasers, tattoos are removed successfully with minimal risk of scarring and permanent pigmentary alterations. Even multicoloured tattoos can be treated successfully and with a low rate of side-effects.
Adolescent↗
A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant recipients.
BACKGROUND: Transplant recipients have an increased propensity to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma. OBJECTIVE: To evaluate the efficacy and tolerability of topical photodynamic therapy with the new highly tumour-selective photosensitizer methyl aminolaevulinate vs. placebo in the treatment of actinic keratoses in transplant recipients. METHODS: Seventeen transplant recipients with a total number of 129 mild to moderate actinic keratoses were enrolled in a prospective, randomized, double-blind, placebo-controlled study. Two lesional areas within a patient were randomized for two consecutive treatments of topical photodynamic therapy 1 week apart using either methyl aminolaevulinate or placebo cream. Sites were illuminated with 75 J cm(-2) of visible light delivered at 80 mW cm(-2) by a noncoherent light source. Complete resolution and reduction in the number or size of actinic keratoses within the lesional area relative to the initial findings were evaluated at weeks 4, 8 and 16 after treatment. RESULTS: The lesional areas treated with methyl aminolaevulinate were clinically cleared in 13 of 17 patients at 16 weeks. A partial response was recorded in a further three. No reduction in the size or number of actinic keratoses was observed in one area treated with methyl aminolaevulinate and in all placebo-treated areas. Adverse events, such as erythema, oedema and crust formation, were mild to moderate, and treatment was well tolerated by all patients. CONCLUSION: Photodynamic therapy using methyl aminolaevulinate is a safe and effective treatment for actinic keratoses in transplant recipients. It may also reduce the risk of transformation of actinic keratoses to invasive, potentially fatal, squamous cell carcinoma.
Adult↗
Survival and prognostic factors in patients with brain metastases from malignant melanoma.
AIM: We wanted to determine the factors influencing survival in a retrospective review of patients with melanoma brain metastases to permit more specific recommendations regarding therapy. PATIENTS AND METHODS: We reviewed the data of 100 patients treated at the Department of Dermatology and Radiation Oncology, University of Zurich, and the Klinik im Park, Zurich. Information on potential prognostic factors (age, sex, location of the primary tumor, Clark level, Breslow index, histological type, number of brain metastases, stage at initial diagnosis, location of brain metastases, and therapy) was collected from the medical records of 100 patients treated between 1966 and 2002. Univariate and multivariate analyses were performed to identify significant prognostic factors. RESULTS: The overall median survival time was 4.8 months, with 6-month, 1-year and 2-year survival percentages of 36, 14 and 5%, respectively. Univariate analysis indicated that survival correlated significantly with radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy, Clark level and Breslow index. Treatment with temozolomide (p = 0.052) and number of brain metastases (p = 0.07) failed to be statistically significant. Multivariate analysis confirmed radiotherapy (partial and whole brain), surgery, stereotactic radiosurgery, chemotherapy and the location of brain metastases as independent and significant prognostic factors of survival. The remaining factors did not reach statistical significance in multivariate analysis. CONCLUSION: Radiotherapy, chemotherapy and especially surgery and stereotactic radiosurgery seem to significantly prolong survival, as shown by multivariate analysis. Treatment with temozolomide will possibly play an important role in the future management of patients with brain metastases from cutaneous melanoma, but further prospective studies to verify this assumption are urgently needed.
Adolescent↗
Combination of bexarotene and psoralen-UVA therapy in a patient with Mycosis fungoides.
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Anticarcinogenic Agents↗
The spectrum of mesenchymal skin neoplasms reflected by the new WHO classification.
Mesenchymal tumors are a heterogeneous group of tumors often arising in the skin and soft tissue. The tumors have been reclassified by the WHO in 2002. Benign mesenchymal tumors are about a hundred times more frequent than malignant mesenchymal tumors. Clinically, mesenchymal tumors often present as skin-colored nodes. Overall, elderly persons are more affected than younger individuals. The etiology is often unknown, sometimes there is an association with insults such as radiation, scars, or lymphedematous or venous stasis. Whereas some years ago a wide excision with a margin of 3-5 cm was performed for malignant variants, today micrographic surgery is preferred, as it can avoid mutilating procedures. Early detection and removal is critical since mesenchymal skin tumors often cannot be cured by radiation or chemotherapy.
Humans↗
Photodynamic therapy--a new treatment option for epithelial malignancies of the skin.
Photodynamic therapy (PDT) is based on the activation of a photosensitizer by illumination with visible light, leading to photochemical tissue destruction or immunomodulation. The greatest disadvantage of systemic administration of photosensitizers is cutaneous photosensitization of the patients, which lasts for some months. An alternative approach for epithelial precancerous lesions, such as actinic keratoses and Bowen's disease, as well as for superficial skin tumors, such as basal cell carcinomas, is the topical application of sensitizers, especially 5-aminolevulinic acid. Topical PDT causes selective tissue necrosis and tumor destruction and produces excellent cosmetic results. The following article summarizes the main principles of PDT and provides a synopsis of the present status of the use of PDT for epithelial skin malignancies.
Aminolevulinic Acid↗
[Cutaneous neoplasms].
The skin is the organ most commonly affected by malignancies. Various cancers of the skin show a dramatic increase in incidence over the last decades. Epithelial skin tumors are most frequently, e.g., basal cell carcinoma and the squamous cell carcinoma with its precursors, the actinic keratoses. Melanoma, which is extremely difficult to treat in advanced tumor stages, is dreaded. Besides that, there are other epithelial malignant diseases, e.g. Morbus Bowen and adnexal tumors originating from the skin appendices. Mesenchymal malignant neoplasias such as Morbus Kaposi, angiosarcomas and other dermal sarcomas, are rare. Since the majority of malignant neoplasms is removable and curable by a simple surgical intervention, the knowledge of the different skin tumors is essential for non-dermatologist.
Adjuvants, Immunologic↗
Necrolytic migratory erythema (glucagenoma)-like skin lesions induced by EGF-receptor inhibition.
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Carcinoma, Non-Small-Cell Lung↗
[Standard and experimental therapy of cutaneous T-cell lymphoma].
Cutaneous T-cell lymphoma represent a heterogeneous group of diseases characterized by skin invasion of monoclonal T-lymphocytes. These cutaneous T-cell lymphomas are divided into 3 groups based on clinical, histological and immunohistological characteristics: Indolent with a survival time of over 10 years, aggressive with a survival time less than 10 years and provisional (EORTC classification). Standard treatments such as PUVA, total skin electron beam, methotrexate, polychemotherapy regimens, retinoids and photopheresis have been used for years. Bexarotene is a newly registered drug. To achieve better response rates, several new drugs are being evaluated in clinical trails, including imiquimod, denileukon-diftitox, liposomal doxorubicin, adeno-interferon-gamma and various combination approaches.
Adrenal Cortex Hormones↗