Cationic solid lipid nanoparticles (cSLN): structure, stability and DNA binding capacity correlation studies.

Cationic solid lipid nanoparticles (cSLN) are promising lipid nanocarriers for intracellular gene delivery based on well-known and widely accepted materials. cSLN containing single-chained cationic lipid cetyltrimethylammonium bromide were produced by high pressure homogenization and characterized in terms of (a) particle size distribution by photon correlation spectroscopy (PCS) and laser diffractometry (LD), (b) thermal behaviour using differential scanning calorimetry (DSC) and (c) the presence of various polymorphic phases was confirmed by X-ray diffraction (WAXD). SLN composed of Imwitor 900P (IMW) showed different pDNA stability and binding capacity in comparison to those of Compritol 888 ATO (COM). IMW-SLN, having z-ave=138-157 nm and d(0.5)=0.15-0.158 µm could maintain this size for 14 days at room temperature. COM-SLN had z-ave=334 nm and d(0.5)=0.42 µm on the day of production and could maintain similar size during 90 days. IMW-SLN revealed improved pDNA binding capacity. We attempted to explain these differences by different interactions between the solid lipid and the tested cationic lipid.

The role of radiation therapy and chemotherapy in the treatment of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare and highly aggressive skin tumor. The purpose of this study was to determine the role of radiation therapy and chemotherapy in the treatment of patients with Merkel cell carcinoma. METHODS: A retrospective analysis of 27 patients treated at Rabin Medical Center in Israel is presented, focusing on the treatment details. Data for 40 patients (the authors' 27 patients and an additional 13 patients from the Israeli Cancer Registry), were analyzed for prognostic factors using univariate and multivariate analyses. RESULTS: Univariate analyses revealed regional lymph node involvement and the coexistence of a second primary tumor as unfavorable prognostic factors. On multivariate analysis, only lymph node involvement showed borderline statistical significance. Radiation therapy was highly effective when given as consolidation after surgery or chemotherapy. In 11 patients irradiated effectively, only 1 (9%) in-field recurrence occurred. Radiation therapy yielded responses in 15 of 15 measurable sites (5 complete responses and 10 partial responses). Chemotherapy produced responses in 18 of 26 patients (69%), mostly complete (41%). However, in the absence of radiation therapy, the responses were short lived. CONCLUSIONS: These data support the use of combined treatment with chemotherapy followed by radiation therapy for patients with advanced locoregional Merkel cell carcinoma. In patients with metastatic disease, chemotherapy as well as radiotherapy can provide effective palliation. Further large scale investigations are warranted to confirm this approach.

Correlation between tps and cea in patients with colorectal-cancer.

Serum TPS and CEA levels were measured in 173 cancer patients with various disease stages. The patients were divided into 4 groups: preoperative group, 16 patients in whom TPS and CEA were measured pre- and postoperatively; group I, 66 newly diagnosed patients up to 40 days post surgery; group II, 86 patients whose blood was taken 40-365 days post surgery, and group III, 47 patients on long-term follow-up in whom blood was taken more than one year after surgery. The median preoperative TPS levels were significantly higher (p<0.01) than the postoperative levels. Patients with Dukes' D had significantly higher TPS (p<0.01) and CEA levels as compared to patients with Dukes' B or C. For both Dukes' B and C stages there was a significant increase in median TPS level between group I and II and III. There was no similar increase in median CEA level. Serial measurements in individual patients show a significant increase in TPS levels between groups I, II and III. In Dukes' D patients, individual TPS levels decreased in response to therapy. There was a significant correlation between TPS and CEA levels. These results suggest that TPS measurement is additive to CEA in follow-up of asymptomatic patients, and to monitor response to therapy in patients with metastatic disease.

Malignant fibrous histiocytoma of the vagina and vulva successfully treated by combined chemotherapy and radiotherapy.

Combined vaginal and vulvar malignant fibrous histiocytoma has not been reported previously. Radical vulvectomy with node dissection is the currently recommended therapy for a vulvar lesion of this type. We present a case with complete tumor regression after combined chemotherapy and radiotherapy. The surgical approach in our patient was inappropriate due to advanced disease. Follow-up examinations for 6 years after initiation of therapy showed no evidence of local recurrence or distant metastasis. Chemotherapy followed by radiotherapy should be considered as an alternative to surgery in patients with advanced vaginal and vulvar involvement and in patients in whom complex medical problems preclude extensive surgical procedures.

Expression of HLA class I and class II in gastric carcinoma in relation to pathologic stage.

The expression of HLA class I and II antigens was studied in 41 patients with gastric cancer and in 2 normal stomachs. The normal gastric epithelia were diffusely stained for class I antigens. No staining was observed for class II. In gastric cancer an overall reduction in staining was observed, which was related to the degree of tumor penetration through the gastric wall. In tumors which penetrated the mucosa and submucosa only, 80-90% of tumor cells were stained for class I, as well as the normal areas surrounding the tumor. On the other hand, in tumors which penetrated through the organ to the fat, only 10-20% of cells were stained. Staining for class II was observed in only 12 cases, all of them advanced, with penetration to muscle or fat. No staining was observed in the normal areas surrounding the tumor. The importance of HLA antigens in immune surveillance is discussed.

Recombinant interleukin-2-activated intracavitary lymphocytes: phenotypic characteristics and effector function.

A preclinical study of intracavitary lymphocytes (ICL) from malignant effusions of cancer patients is described. The object of this study was to evaluate the antitumor potential of ICL as a baseline for developing adoptive immunotherapy trial for ovarian carcinoma patients. The main parameters studied were functional cytolytic activity of fresh and recombinant interleukin-2 (rIL-2)-activated ICL and their phenotypic characteristics. Spontaneous cytolytic activity of ICL was detected in all samples tested against natural killer (NK)-sensitive targets (K562), while very low activity was shown against NK-resistant targets (Daudi) and fresh tumor cells. Activation in culture with rIL-2 generated cytolytic activity against NK-resistant targets and significantly augmented NK activity. The pattern of antitumor lytic activity of ICL resembles lymphokine-activated killer cell activity and is non-major histocompatibility complex restricted against a variety of tumor targets. Phenotypic characterization of fresh ICL showed the predominance of CD3+ cells with the CD4/CD8 ratio resembling that of peripheral blood lymphocytes. During culture with rIL-2, changes in phenotypic expression of activated ICL were detected: enrichment in NKH1+ cells (up to 65%), of CD8+ (up to 70%), and very late antigen (VLA)-1+ cells (up to 54%), concomitantly with a decrease in CD4+ population. The NKH1, CD8, and VLA-1 expression peaked at 2 weeks in culture and coincided with peak cytolytic activity of cultured ICL. Depletion of CD8+ cells from activated ICL resulted in a decreased proportion of cells expressing the NKH1 and VLA-1 phenotype, whereas depletion CD4+ cells led to enrichment in CD8, NKH1, and VLA-1 antigens. Cytolytic activity was significantly increased in CD4 depleted population against NK-resistant and NK-sensitive targets. In this study we found that rIL-2 activation and culture of ICL generates killer activity against NK-resistant and fresh tumor targets and that enrichment in expression of NKH1, CD8, and VLA-1 antigens is associated with effector function.

A pilot study of intraperitoneal recombinant interleukin-2 and ex vivo activated intracavitary lymphocytes in patients with malignant peritoneal spread: I. Clinical aspects.

A novel approach to adoptive immunotherapy is described in this study. Of 13 patients with malignant effusions, nine were treated by intraperitoneal (IP) instillation of intracavitary lymphocytes (ICL), activated ex vivo by recombinant interleukin-2 (rIL-2, Cetus Co., Emeryville, CA) with escalating doses of IP rIL-2 and four by IP rIL-2 alone. ICL and rIL-2 were administered by repeated peritoneal punctures. Patients were divided into two groups: group I of six patients, who received activated ICL with low doses of IP rIL-2 (total dose not exceeding 6 X 10(5) units) and group II of seven patients, in whom escalating higher doses of rIL-2 were administered IP with or without activated ICL, in doses ranging from 10(6) up to 16 X 10(6) units, total dose. Total dose of ICL given ranged from 2 X 10(8) to 2 X 10(9) in both groups. The main objectives of this pilot study was to establish the feasibility of treatment by ex vivo activated ICL and IP rIL-2, to assess the toxicity associated with such a treatment, to escalate doses of rIL-2 to a maximal tolerable dose, and to look for clinical responses. The first two goals were achieved: such a treatment approach is feasible and is not associated with severe toxicity. The side effects observed during this study were usually mild in group I patients and more pronounced in group II patients. These included transient fever, chills, nausea, cellulitis at the puncture site, and one case of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)