Immune rejection of a large sarcoma following cyclophosphamide and IL-12 treatment requires both NK and NK T cells and is associated with the induction of a novel NK T cell population.

Combined immunotherapy with cyclophosphamide (Cy) and IL-12, but not IL-12 alone, stimulates eradication of a large established solid tumor (20 mm), MCA207, a methylcholanthrene-induced murine sarcoma. In these studies we demonstrate that NK1.1(+) cells and CD1d-dependent NK T cells each play important yet distinct roles in regression of a large tumor in response to Cy and IL-12, and we define a novel NK T cell subset, selectively increased by this treatment. Mice depleted of NK1.1(+) cells demonstrated more rapid initial tumor growth and prolonged tumor regression following treatment, but tumors were eventually eradicated. In contrast, initial tumor regression following therapy was unimpaired in CD1d(-/-) mice, which are deficient in most NK T cells, but tumors recurred. No tumor regression occurred following Cy and IL-12 therapy in CD1d(-/-) mice that were depleted of NK1.1(+) cells. We found that Cy and IL-12 induced the selective increase in liver and spleen lymphocytes of a unique NK T subpopulation (DX5(+)NK1.1(-)CD3(+)). These cells were not induced by treatment in CD1d(-/-) mice. Our studies demonstrate a contribution of both NK and NK T cells to the Cy- and IL-12-stimulated anti-tumor response. We describe the selective induction of a distinct NK T cell subset by Cy and IL-12 therapy, not seen following IL-12 therapy alone, which we suggest may contribute to the successful anti-tumor response induced by this immunotherapeutic regimen.

Treosulfan is an effective alkylating cytostatic for malignant melanoma in vitro and in vivo.

The therapy of metastatic malignant melanoma is limited by poor responses and short overall survival. Thus it remains an important issue to identify and test potential new drugs in this disease. This study was performed to examine the effects of the bifunctional alkylating cytostatic treosulfan in vitro. Using an in vitro microplate ATP bioluminescence tumour chemosensitivity assay (ATP-TCA) five highly chemoresistant melanoma cell lines and melanoma cells freshly isolated from metastases surgically resected from stage IV melanoma patients (n = 10) were incubated with treosulfan. Three cell lines and eight of the 10 tested tumour cells isolated from melanoma metasteses showed tumour growth inhibition >50% after incubation with treosulfan. Therefore, 14 patients with rapidly progressing stage IV malignant melanoma who had been pretreated with at least one standard chemotherapy regimen received treosulfan. In this population of patients with highly refractory advanced melanoma, one complete remission (7.1%), two partial remissions (14.3%) and three cases of stable disease (21.4%) were observed. The median survival time for all the patients measured from the beginning of treosulfan treatment was 9 months, and the median overall survival was 17 months. Except for two patients who developed grade 3 leucopenia, only moderate side effects were observed. Therefore, we conclude that treosulfan was well tolerated in this small series of patients and seems to be a promising alkylating cytostatic for the treatment of metastatic melanoma. Further studies are warranted to test these findings.

[Syringocystadenoma papilliferum and trichoblastoma within a sebaceous nevus]. / Syringocystadenoma papilliferum und Trichoblastom innerhalb eines Naevus sebaceus.

Since birth, a 43 year-old man displayed a nevus sebaceus on the right temple. The histopathology revealed two distinct adnexal neoplasms associated with this lesion: a syringocystadenoma papilliferum and a trichoblastoma. We describe the combination of these entities in this report.

[Detection of H-ras and K-ras in tumors of gastrointestinal-pancreatic system]. / Detektion von H-Ras und K-Ras in Tumoren des Gastro-Entero-Pankreatischen Systems (GEP).

The Gastro-Entero-Pancreatic System (GEP) defined a group of highly differentiated neuroendocrine tumors (Insulinomas, Gastrinomas, PP-omas, Somatostatinomas, Carcinoids). In this kind of tumors the multistage carcinogenesis is really unknown. Activated ras oncogenes could play an important role in initiation or process of carcinogenesis in different human cancers. The purpose of our study was to determe if H-ras or K-ras play a role in the carcinogenesis of GEP tumors. 20 paraffin embedded tumor tissues (1 Vipom, 1 Somatostatinom, 10 Carcinoids, 1 Gastrinoma, 4 livermetastasis of a Carcinoid, 3 Insulinomas) were analysed immunohistologic of H-ras and K-ras oncogene protein expression. Immunohistologic investigations showed a H-ras expression in 65% (13/20). K-ras protein could detected in 10% (2/20). On the basis of these data H-ras oncogene expression could play a role in the multistage carcinogenesis of GEP tumors.