Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress.

DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature.

Epidermal Keratinocyte Depletion during Five Weeks of Radiotherapy is Associated with DNA Double-Strand Break Foci, Cell Growth Arrest and Apoptosis: Evidence of Increasing Radioresponsiveness and Lack of Repopulation; the Number of Melanocytes Remains Unchanged.

During fractionated radiotherapy, epithelial cell populations are thought to decrease initially, followed by accelerated repopulation to compensate cell loss. However, previous findings in skin with daily 1.1 Gy dose fractions indicate continued and increasing cell depletion.

High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer.

Purpose: We report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups.

Methods: Proton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications.

UV-Radiation Response Proteins Reveal Undifferentiated Cutaneous Interfollicular Melanocytes with Hyperradiosensitivity to Differentiation at 0.05 Gy Radiotherapy Dose Fractions.

To date, the response activated in melanocytes by repeated genotoxic insults from radiotherapy has not been explored. We hypothesized that the molecular pathways involved in the response of melanocytes to ionizing radiation and ultraviolet radiation (UVR) are similar. Skin punch biopsies, not sun-exposed, were collected from prostate cancer patients before, as well as at 1 and 6.

Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer.

Background: High-dose-rate brachytherapy (HDR-BT) has optimal prerequisites in radiotherapy of prostate cancer (PC) with a conformal dose distribution and high doses per fraction giving a biological dose escalation. We report the outcome after HDR-BT and external beam radiotherapy (EBRT) after 20 years of experience.

Material And Methods: The study includes 623 patients, median age of 66 years, treated from 1995 to 2008 and a median follow up of 11 years (range 2-266 months).

Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy.

Background And Purpose: Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions.

Materials And Methods: 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.

Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy: long-term results from a randomized controlled trial.

Background And Purpose: To evaluate the long-term effects of dietary intervention on gastrointestinal symptoms after highly dose-escalated radiotherapy for localized prostate cancer, using boost with protons or high-dose-rate brachytherapy.

Materials And Methods: Patients were randomized to an intervention group (n=64) advised to reduce insoluble dietary fiber and lactose intake, or to a standard care group (n=66) advised to continue their usual diet. Gastrointestinal symptoms, other domains of health-related quality of life (HRQOL), and dietary intake were evaluated for ⩽24months post-radiotherapy with the European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-C30 and QLQ-PR25, Gastrointestinal Side Effects Questionnaire, and Food Frequency Questionnaire.

Cell senescence in myxoid/round cell liposarcoma.

Myxoid/round cell liposarcoma (MLS/RCLS) is the second most common liposarcoma type and characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases, and their inhibitors but very few cells progressing through the G1/S boundary. Here, we extend the investigation to proteins involved in cell senescence in an immunohistochemistry based study of 17 MLS/RCLS cases.

Assessing patients' perceived bother from the gastrointestinal side effects of radiotherapy for localized prostate cancer: initial questionnaire development and validation.

Background: The present study reports on the development and first steps of validation of the Gastrointestinal Side Effects Questionnaire (GISEQ), a measure of patient-reported gastrointestinal symptoms following local radiotherapy to the prostate. The questionnaire design provides a novel approach of assessment of side effects of prostate radiotherapy, by enabling measurement of patient-perceived change in symptoms.

Material And Methods: The eight-item GISEQ was administered to 130 prostate cancer patients referred to radiotherapy.

Whole-body diffusion-weighted MRI compared with (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate carcinoma.

Objective: The purpose of this study was to evaluate the accuracy of whole-body diffusion-weighted MRI (DWI) and (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate cancer.

Subjects And Methods: Both patient- and lesion-based analyses were performed on 49 consecutive patients (median age, 67 years; age range, 57-80 years) with recently diagnosed high-risk prostate cancer. All patients underwent bone scintigraphy, whole-body MRI including DWI and (18)F-NaF PET/CT before treatment.

Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer.

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months.

Effects of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life: a randomized controlled trial in prostate cancer patients undergoing radiotherapy.

Purpose: To study the effect of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life (HRQOL) in prostate cancer patients referred to radiotherapy.

Materials And Methods: A total of 130 patients were randomly assigned to one of two groups: an intervention group (IG, n=64), instructed to reduce their intake of insoluble dietary fibres and lactose, a standard care group (SC, n=66), instructed to continue their normal diet. Gastrointestinal side effects and other aspects of HRQOL were evaluated from baseline up to 2 months after completed radiotherapy, using the EORTC QLQ-C30 and QLQ-PR25 and the study-specific Gastrointestinal Side Effects Questionnaire (GISEQ).

Direct effects of pure nicotine, cigarette smoke extract, Swedish-type smokeless tobacco (Snus) extract and ethanol on human normal endothelial cells and fibroblasts.

Unlabelled: The adverse health effects of cigarette smoking are well established including the increased risk of various types of cancer. In this study, the direct effects of ethanol, pure nicotine, cigarette smoke extract and Swedish type smokeless tobacco (Snus) extract on normal cells were investigated.

Materials And Methods: Primary normal adult human endothelial cells and fibroblasts at early passage were used.

Imaging tumor perfusion and oxidative metabolism in patients with head-and-neck cancer using 1- [11C]-acetate PET during radiotherapy: preliminary results.

Background: A growing body of in vitro evidence links alterations of the intermediary metabolism in cancer to treatment outcome. This study aimed to characterize tumor oxidative metabolism and perfusion in vivo using dynamic positron emission tomography (PET) with 1- [(11)C]-acetate (ACE) during radiotherapy.

Methods And Materials: Nine patients with head-and-neck cancer were studied.

DNA content and methylation of p16, DAPK and RASSF1A gene in tumour and distant, normal mucosal tissue of head and neck squamous cell carcinoma patients.

Unlabelled: Long-term survival of head and neck squamous cell carcinoma (HNSCC) patients has not improved significantly during the last 20 years and recurrent disease is frequently observed. In this study, the potential presence of pre-malignant cells or rare malignant cells at the time of diagnosis in HNSCC was investigated.

Patients And Methods: Fifty-nine biopsies obtained from 41 HNSCC patients were analysed.

Five-year results from a Scandinavian sarcoma group study (SSG XIII) of adjuvant chemotherapy combined with accelerated radiotherapy in high-risk soft tissue sarcoma of extremities and trunk wall.

Purpose: To evaluate adjuvant chemotherapy and interpolated accelerated radiotherapy (RT) for adult patients with high-risk soft tissue sarcoma in the extremities or trunk wall.

Methods And Materials: High-risk soft tissue sarcoma was defined as high-grade malignancy and at least two of the following criteria: size≥8 cm, vascular invasion, or necrosis. Six cycles of doxorubicin and ifosfamide were prescribed for all patients.

A method to separate the rectum from the prostate during proton beam radiotherapy of prostate cancer patients.

Unlabelled: The use of protons for curative treatment of prostate cancer is increasing, either as a single treatment modality or in combination with conventional radiotherapy. The proximity between prostate (target) and rectum (organ at risk) often leads to a compromise between dose to target and organ at risk.

Material And Methods: The present study describes a method where the distance between prostate and rectum is increased by retraction of the rectum in dorsal direction.

A low-dose hypersensitive keratinocyte loss in response to fractionated radiotherapy is associated with growth arrest and apoptosis.

Background And Purpose: The existence of a hypersensitive radiation response to doses below 0.5Gy is well established for many normal and tumour cell lines. There is also evidence for hypersensitive tissue responses in acute skin damage and kidney function in mice.

In vitro effect of radiation, antibody to epidermal growth factor receptor and Docetaxel in human head and neck squamous carcinoma cells with mutant P53 and over-expressed EGFR.

Purpose: Radiotherapy is the most frequently used and cheapest treatment both for curative and palliative purposes in HNSCC. Despite advances in technology and intensive treatments with radiation, only half of the patients are cured. New therapeutic approaches focusing on the molecular mechanism that mediate tumour cell growth or cell death in combination with radiotherapy have been suggested.

Optimizing treatment for men with advanced prostate cancer: expert recommendations and the multidisciplinary approach.

A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice.

Low-dose hypersensitive gammaH2AX response and infrequent apoptosis in epidermis from radiotherapy patients.

Background And Purpose: A low-dose hypersensitivity to radiation can be observed in vitro for many human cell types in terms of increased cell kill per dose unit for doses below 0.5Gy. Quantification of the double-strand break marker gammaH2AX in samples taken in clinical radiotherapy practice has the potential to provide important information about how induction and repair of severe DNA damage and apoptosis are linked to low-dose hypersensitivity.

Human papillomavirus (HPV), DNA aberrations and cell cycle progression in anal squamous cell carcinoma patients.

Unlabelled: Human papillomavirus (HPV) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated.

Patients And Methods: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients' biopsies.

1-[11C]-acetate PET imaging in head and neck cancer--a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning.

Purpose: The aim of this study was to evaluate the feasibility of using 1-[(11)C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using (18)F-fluoro-2-deoxy-D: -glucose (FDG) PET.

Methods: Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart.