Esophageal squamous cell cancer in patients with head and neck cancer: Prevalence of human papillomavirus DNA sequences

An etiologic role for human papillomavirus (HPV) infections in either head and neck (HNC) or esophageal carcinogenesis remains debatable. Patients with head and neck cancer are at high risk for developing a second esophageal squamous cell cancer (ESCC). The aim of our study was to determine whether HPV infections play a role in this multifocal carcinogenesis. Samples from 2 groups of HNC patients were studied: Random esophageal biopsies were collected from the first group of 60 patients who had been screened for asymptomatic ESCC. The second group consisted of 21 patients with pairs of HNC and ESCC. Both the fresh frozen biopsy samples of the first group and the paraffin-embedded specimens of the second group were evaluated for the presence of HPV DNA sequences by PCR amplification, cloning and sequencing. HPV DNA sequences were detected in 66.7% of normal/inflammatory (34/51) and dysplastic and malignant (6/9) esophageal tissues from HNC patients being screened endoscopically. Similarly, in the second group of 21 patients with both HNC and ESCC, HPV DNA sequences were demonstrated in 13 (61.9%) of the HNC biopsies and in 14 (66.7%) of the ESCC biopsies. The prevalence of high-risk-type HPV 16 was low (5/51, 9.8%) in normal/inflammatory esophageal mucosa but higher (10/24, 47.6%) in ESCC. The low-risk HPV 11 was present in 37.3% (19/51) of normal/inflammatory, 66.7% (4/6) of dysplastic and 28.9% (13/45) of the carcinoma samples. The same HPV type was present in only 3/21 pairs of HNC and ESCC samples, suggesting that a clonal expansion from the HNC to a subsequent ESCC, or visa versa, is unlikely. The high prevalence of "low-risk" HPV infections points to the need for studies on possible interactions of these infections with the use of alcohol and tobacco in the pathogenesis of these tumors.     

PET-CT und interventionelle Tumortherapie

Multifocal metastatic spread of solid tumours is often a diagnostic and therapeutic challenge. Those patients often cannot undergo curative surgery. Since several years, various types of interventional tumour therapy have been introduced, which may represent a promising option in those cases. In some cases morphological imaging is not able to assess the viability of a previously treated lesion.The combination of computed tomography and positron emission tomography has the potential to ease planning and guiding of interventional procedures and to improve postinterventional control. Due to its higher sensitivity and specificity, PET/CT enables for a more precise selection of patients for interventional tumor therapy. The success of a particular therapy could be assessed with greater accuracy using PET/CT as compared with the separate modalities. PET/CT was also able to improve planning and guiding interventional therapy. As of yet, no data are available concerning the success rate and long-term survival of PET/CT associated interventional procedures.     

CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems

Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration.     

Targeting osseous metastases: Rationale and development of radioimmunotherapy for prostate cancer

For patients with metastatic prostate cancer, bone is the primary site of tumor localization and the major cause of disease-related morbidity and mortality. Hormonal therapy and chemotherapy alone cannot eradicate disease harbored in bone. The delivery of radiotherapy to the reservoir of disease is an approach previously only achievable using bone-seeking radiopharmaceuticals. Now, however, with the identification of tumor-specific targets, antibodies are being used to deliver radiotherapy to these sites. In this article, we review the rationale behind this approach, the targets being explored, the radiation sources available, and the antibodies currently under clinical development.     

Effects of amifostine on clonogenic mesenchymal progenitors and hematopoietic progenitors exposed to radiation

PURPOSE: To determine the radiation sensitivities of mesenchymal progenitors and hematopoietic progenitors, and to determine the in vitro effects of amifostine on hematopoietic and mesenchymal progenitors exposed to radiation. METHODS: Radiosensitivity of mesenchymal progenitor cells was determined by exposing marrow low-density cells to radiation at doses of 100 to 800 cGy. Mesenchymal cell colonies were established by plating 2.5 x 10(5) marrow low-density cells in long-term marrow culture medium (LTCM). The size, frequency, and cellular composition of the mesenchymal progenitor cells were scored after 14 days of incubation. Mesenchymal progenitor cells were subdivided into progenitors forming fibroblast and adipocyte mixed colonies (CFU-FA), and pure fibroblast colonies (CFU-F). Hematopoietic progenitors were assessed by methylcellulose-based assay. RESULTS: Radiation at 100 cGy caused a mild decrease in CFU-F and CFU-FA derived colonies by 12% and 13%, respectively; 200 cGy decreased CFU-F by 36% and CFU-FA by 52%; 400 cGy decreased CFU-F by 50% and CFU-FA by 86%; and 600 cGy decreased CFU-F by 24%, with total absence of CFU-FA. Pretreatment with amifostine protected 100% of CFU-F at 100 and 200 cGy, 84% at 400 cGy, 46% at 600 cGy, and 14% at 800 cGy. With CFU-FA colonies amifostine pretreatment provided only minimal radioprotection. For hematopoietic progenitors radiation at 100 cGy reduced CFU-GM by 74% but had no significant effect on CFU-GEMM and BFU-E. Radiation at 200 cGy decreased CFU-GEMM by 72%, BFU-E by 54%, and CFU-GM by 84%; 400 cGy further decreased CFU-GEMM by 83%, BFU-E by 81%, and CFU-GM by 93%. Pretreatment with amifostine resulted in twofold stimulation of CFU-GEMM and BFU-E colonies. All BFU-E colonies were protected up to 200 cGy. For CFU-GEMM amifostine pretreatment resulting in 68% at 200 cGy and 31% at 400 cGy. For CFU-GM colonies it was 54% at 100 cGy, 32% at 200 cGy, and 12% at 400 cGy. CONCLUSIONS: Mesenchymal progenitor cell subpopulations are differentially sensitive to radiation. Amifostine protects both mesenchymal and hematopoietic progenitors against radiation injury, though the level of protection appears to be dependent upon the sensitivities of these progenitor cells to radiation. Amifostine is a potent stimulant of BFU-E and CFU-GEMM progenitor colonies.     

Migraine headaches and sleep disturbances in children

OBJECTIVE: The aim of the present study was to investigate the prevalence of sleep disturbances in children with migraine headaches and to describe individual differences in sleep behaviors based on headache features (eg, frequency, duration, intensity). BACKGROUND: A relationship between migraine headaches and sleep disturbances has been suggested in both children and adults, but there is a lack of research examining the relationship between specific headache features and the range of sleep behaviors in children. METHODS: One hundred eighteen children, aged 2 to 12 years (mean, 9.1; standard deviation, 2.3) were evaluated for headaches at two pediatric neurology departments. Parents completed the Children's Sleep Habits Questionnaire and a standardized questionnaire regarding headache characteristics. RESULTS: Parents reported a high rate of sleep disturbances in children, including sleeping too little (42%), bruxism (29%), child co-sleeping with parents (25%), and snoring (23%). Children with migraine headaches experienced more sleep disturbances compared to published healthy control norms. After controlling for child demographics, we found that the frequency and duration of migraine headaches predicted specific sleep disturbances, including sleep anxiety, parasomnias, and bedtime resistance. CONCLUSIONS: Children with migraine headaches have a high prevalence of sleep disturbances. The direction of the relationship between headaches and sleep is unknown. Regardless, interventions targeting sleep habits may improve headache symptoms, and effective treatment of headaches in children may positively impact sleep.