Differences in dendritic cell activation and distribution after intravenous, intraperitoneal, and subcutaneous injection of lymphoma cells in mice.

Dendritic cells (DCs) are key antigen-presenting cells (APCs) for initiating immune responses. However, in recent years, several groups have shown the defective function of DCs in tumor-bearing mice and in cancer patients. Our aim was to study the effects of lymphoma on DC differentiation and maturation and to assess the input of the tumor microenvironment and intravasation of tumor cells on DC precursors. EL-4 lymphoma cells were administrated via different routes (intraperitoneal, subcutaneous, and intravenous) and DC phenotype was investigated. Bone marrow-derived DCs and APCs obtained from the spleen were examined by flow cytometry, and immunohistochemical analysis of lymphoma, lungs, livers, and spleens was also performed. Intravenous administration of lymphoma cells induced suppression of DC differentiation and maturation assessed as a significant decrease of the IAb, CD80, CD86, CD11b, and CD11c expression on DCs and IAb on splenic APCs. Upregulation of APC differentiation was observed in animals after subcutaneous and intraperitoneal administration of lymphoma cells determined as increased expression of CD40 and CD86 in spleen APCs. These data suggest that the development of antitumor immune response might differ in the host receiving tumor vaccines via different injection routes.

Children and partners of patients with recurrent respiratory papillomatosis have no evidence of the disease during long-term observation.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract. The aim of our study was to investigate whether children and partners of patients with RRP develop the same disease and to determine whether there is an impact of pregnancy on the course of RRP. PATIENTS AND METHODS: Thirty-eight of 42 patients with RRP were accepted for a multicenter prospective study in Germany in 21.06.83-12.03.90. Mean follow-up duration was 15.3+/-1.8 years. The data of partners of patients with RRP was collected during the period of observation and then updated via interviews in January 2006. Twenty-nine children and four grandchildren were born to 14 patients with RRP. Fifteen of 448 cases of patients with RRP were treated in Saint Vladimir Moscow Children's Hospital in Russia in 1988-2003 and analyzed retrospectively. Sixteen children and one grandchild were born to 15 patients with RRP from Russia. In both studies, the virus type of patients with RRP was identified by nested PCR or Southern blot hybridization. Statistical analysis was performed using Fisher's exact test (probability value set at p<0.05). RESULTS: All children born to patients with RRP were healthy. RRP was not diagnosed in any of them on the basis of clinical or histological examination. Four of 45 children developed dysphonia, two of them had vocal cord nodules. None of the sexual partners of patients has developed RRP during the follow-up period. Pregnancy was accompanied by excessive growth of papillomas in all women (100%) with RRP associated with HPV type 11, and only in 16.7% of women with RRP associated with HPV type 6 (p=0.001). CONCLUSIONS: Patients with RRP are able to have healthy children regardless of the stage of the disease. Partners of RRP patients do not develop RRP during an observation period of 15 years. Pregnancy has a negative impact on the course of RRP and local laryngeal status in patients; it is more significant in HPV type 11 associated cases as it is manifested by more rapid papillomas growth and more frequent recurrence.

Human papilloma virus (HPV)-associated gynecological alteration in mothers of children with recurrent respiratory papillomatosis during long-term observation.

BACKGROUND: Human papilloma virus (HPV) is one of the most frequently observed sexually transmitted infections. The study' purpose was to investigate the relation between a mother's gynecological history and the local status of her child with recurrent respiratory papillomatosis (RRP). METHODS: Forty-two patients enrolled in a prospective multicenter study between 1983 and 1990. The study included patients with juvenile-onset and adult-onset RRP. All patients underwent surgery and treatment with alpha-interferon. Thirty-eight patients were followed up until 31.01.2006. Twenty-five mothers of these patients participated in a parallel prospective study of genital HPV infection. In 1989-1990, all received a routine gynecological examination, an expanded colposcopy, a Pap smear, and a cervical biopsy. The mothers were followed up until February 2006. RESULTS: 74% of patients with RRP were the first-born children. Five (20%) mothers had condylomata acuminata, newly diagnosed during pregnancy. Indicators of HPV infection such as koilocytes, koilocytotic dysplasia and condyloma acuminatum were revealed cytologically in 17% of cases and histologically in 71.4% of cases. Six (24%) of mothers had had a hysterectomy. HPV type 11 was prevalent in the children of mothers who had had a hysterectomy. Among the patients with juvenile-onset RRP, the death rate from squamous cell carcinoma of the lung was significantly higher in those patients whose mothers had a hysterectomy (p=0.028). CONCLUSIONS: Mothers of patients with RRP demonstrated cytological and histological indicators of HPV infection in the genital tract. An adverse outcome of the disease in the child was associated with adverse gynecological history in the mother.