Liposarcoma cells with aldefluor and CD133 activity have a cancer stem cell potential

Aldehyde dehydrogenase (ALDH) has recently been shown to be a marker of cancer stem-like cells (CSCs) across tumour types. The primary goals of this study were to investigate whether ALDH is expressed in liposarcomas, and whether CSCs can be identified in the ALDHhigh subpopulation. We have demonstrated that ALDH is indeed expressed in 10 out of 10 liposarcoma patient samples. Using a liposarcoma xenograft model, we have identified a small population of cells with an inducible stem cell potential, expressing both ALDH and CD133 following culturing in stem cell medium. This potential CSC population, which makes up for 0, 1-1, 7% of the cells, displayed increased self-renewing abilities and increased tumourigenicity, giving tumours in vivo from as few as 100 injected cells

Temporal bone verrucous carcinoma: outcomes and treatment controversy

Verrucous carcinoma is a rare tumor that presents in the head and neck with the most common sites being the oral cavity and larynx. Fourteen cases of verrucous carcinoma of the temporal bone have been described in literature; this study aims to examine treatment outcomes and discuss the controversy surrounding postoperative radiation. The study design included a literature review along with individual case report in the setting of a tertiary care medical center. Outcome analysis of all cases of verrucous carcinoma of the temporal bone, which are documented in the English literature, and presentation of a single patient report including gross, histologic and radiologic analyses were performed. The longest recorded survival for verrucous carcinoma of the temporal bone occurs in patients treated with surgery alone. Poorer outcomes for patients treated with adjuvant (chemo)radiation may be due to more advanced stage of disease at the time of treatment. Early reports of radiation leading to tumor dedifferentiation or early recurrence are not supported by more recent studies. Whether adjuvant radiation therapy is indicated in verrucous carcinoma of the temporal bone remains controversial

Dropout in a longitudinal, cohort study of urologic disease in community men

BACKGROUND: Reasons for attrition in studies vary, but may be a major concern in long-term studies if those who drop out differ systematically from those who continue to participate. Factors associated with dropout were evaluated in a twelve-year community-based, prospective cohort study of urologic disease in men. METHODS: During 1989–1991, 2,115 randomly selected Caucasian men, ages 40–79 years from Olmsted County, Minnesota were enrolled and followed with questionnaires biennially; 332 men were added in follow-up. A random subset (~25%) received a urologic examination. Baseline characteristics including age, benign prostatic hyperplasia (BPH) symptoms, comorbidities, and socioeconomic factors were compared between subjects who did and did not participate after the twelfth year of follow-up. RESULTS: Of the 2,447 men, 195 died and were excluded; 682 did not participate in 2002. Compared with men in the 40–49 year age group, men ≥ 70 years of age at baseline had a greater relative odds of dropout, 2.65 (95% CI: 1.93, 3.63). In age-adjusted analyses, relative to men without stroke, men who had suffered a stroke had a higher odds of dropout, age-adjusted OR 3.07 (95% CI: 1.49, 6.33). Presence of at least one BPH symptom was not associated with dropout, (age-adjusted OR 1.12 (95% CI: 0.93, 1.36)). CONCLUSION: These results provide assurance that dropout was not related to primary study outcomes. However, factors associated with dropout should be taken into account in analyses where they may be potential confounders

Diagnosis of Partial Body Radiation Exposure in Mice Using Peripheral Blood Gene Expression Profiles

In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB) can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI). However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79–100%) compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16–43%), suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation

Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer

Introduction The BRCA1 protein makes mammary stem cells differentiate into mature luminal and myoepithelial cells. If a BRCA1 mutation results in a differentiation block, an enlarged stem cell component might be present in the benign tissue of BRCA1 mutation carriers, and these mammary stem cells could be the origin of BRCA1 related breast cancer. Since ALDH1 is a marker of both mammary stem cells and breast cancer stem cells, we compared ALDH1 expression in malignant tissue of BRCA1 mutation carriers to non-carriers. Methods Forty-one BRCA1 related breast cancers and 41 age-matched sporadic breast cancers were immunohistochemically stained for ALDH1. Expression in epithelium and stroma was scored and compared. Results Epithelial (P=0.001) and peritumoral (P=0.001) ALDH1 expression was significantly higher in invasive BRCA1 related carcinomas compared to sporadic carcinomas. Intratumoral stromal ALDH1 expression was similarly high in both groups. ALDH1 tumor cell expression was an independent predictor of BRCA1 mutation status. Conclusion BRCA1 related breast cancers showed significantly more frequent epithelial ALDH1 expression, indicating that these hereditary tumors have an enlarged cancer stem cell component. Besides, (peritumoral) stromal ALDH1 expression was also more frequent in BRCA1 mutation carriers. ALDH1 may therefore be a diagnostic marker and a therapeutic target of BRCA1 related breast cancer

Alternative implication of CXCR4 in JAK2/STAT3 activation in small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive, rapidly metastasising tumour. Previously, we demonstrated the influence of CXCL12–CXCR4 interaction on processes involved in metastasis and chemoresistance in SCLC. We show here that STAT3 is expressed in both primary SCLC tumour tissues and SCLC cell lines. We investigated the function of STAT3 upon CXCL12 stimulation in SCLC cell lines. Small cell lung cancer cell lines present constitutive phosphorylation of STAT3, and in the reference cell lines NCI-H69 and NCI-H82 constitutive phosphorylation was further increased by CXCL12 stimulation. Further investigating this signalling cascade, we showed that it involves interactions between CXCR4 and JAK2 in both cell lines. However CXCL12-induced adhesion to VCAM-1 could be completely inhibited by the JAK2 inhibitor AG490 only in NCI-H82. Furthermore, CXCR4 antagonist but not AG490 inhibited cell adhesion whereas both antagonisms were shown to inhibit growth of the cells in soft agar, indicating the central involvement of this signalling in anchorage-independent growth of SCLC cells. Most interestingly, while using primary tumour material, we observed that in contrast to non-small-cell lung cancer samples from primary tumour tissues, all analysed samples from SCLC were strongly positive for tyrosine-phosphorylated STAT3. Taken together, these data indicate that STAT3 is constitutively phosphorylated in SCLC and is important in SCLC growth and spreading thus presenting an interesting target for therapy