CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers that still lacks effective treatments. Dysregulation of kinase signaling has frequently been reported to contribute to HCC. In this study, we used bioinformatic approaches to identify kinases that regulate gene expression changes in human HCCs and two murine HCC models. We identified a role for calcium/calmodulin-dependent protein kinases II gamma isoform (CAMK2γ) in hepatocarcinogenesis. CAMK2γ-/- mice displayed severely enhanced chemical-induced hepatocarcinogenesis compared with wild-type controls. Mechanistically, CAMK2γ deletion potentiates hepatic activation of mechanistic target of rapamycin complex 1 (mTORC1), which results in hyperproliferation of hepatocytes. Inhibition of mTORC1 by rapamycin effectively attenuates the compensatory proliferation of hepatocytes in CAMK2γ-/- livers. We further demonstrated that CAMK2γ suppressed growth factor- or insulin-induced mTORC1 activation by inhibiting IRS1/AKT signaling. Taken together, our results reveal a novel mechanism by which CAMK2γ antagonizes mTORC1 activation during hepatocarcinogenesis.

The viral oncogene Np9 acts as a critical molecular switch for co-activating ß-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells.

HERV-K (human endogenous retrovirus type K) type 1-encoded Np9 is a tumor-specific biomarker, but its oncogenic role and targets in human leukemia remain elusive. We first identified Np9 as a potent viral oncogene in human leukemia. Silencing of Np9 inhibited the growth of myeloid and lymphoblastic leukemic cells, whereas expression of Np9 significantly promoted the growth of leukemia cells in vitro and in vivo. Np9 not only activated ERK, AKT and Notch1 pathways but also upregulated ß-catenin essential for survival of leukemia stem cells. In human leukemia, Np9 protein level in leukemia patients was substantially higher than that in normal donors (56% vs 4.5%). Moreover, Np9 protein level was correlated with the number of leukemia stem/progenitor cells but not detected in normal CD34(+) hematopoietic stem cells. In addition, Np9-positive samples highly expressed leukemia-specific pol-env polyprotein, env and transmembrane proteins as well as viral particles. Thus, the viral oncogene Np9 is a critical molecular switch of multiple signaling pathways regulating the growth of leukemia stem/progenitor cells. These findings open a new perspective to understand the etiology of human common leukemia and provide a novel target for treating leukemia.

Male adolescents and physician sex preference.

OBJECTIVE: To investigate the physician sex preference of male adolescents and to explore the factors that may moderate this preference. DESIGN: Anonymous survey. SETTING: An adolescent clinic associated with a large pediatric hospital centrally located within a metropolitan Midwestern city. PARTICIPANTS: The 67 male adolescent patients in the convenience sample ranged in age from 10 to 18 years, and 43.3% were African American, 40.3% were white, and 16.4% were classified as "other." More than half of the subjects reported being raised by a single mother with just enough money to meet their basic needs. INTERVENTION: None. MAIN OUTCOME MEASURES: Among the variables investigated were expressed physician sex preference and participant connectedness to a male and/or female parent or role model. RESULTS: More subjects reported a preference for a female physician (50.8%) than for a male physician (39.4%) when the examination was a physical or medical checkup. The preference for a female physician during a genital examination was also higher (49.2%) than preference for a male physician (39.1%). Analysis of variance revealed significant ethnic group differences in physician sex preference (F2,64 = 12.02, P<.001). African American males had a significantly higher preference for a female physician than did whites or those who identified themselves as other. Neither socioeconomic status nor age demonstrated a statistically significant effect. CONCLUSIONS: This preliminary investigation has provided evidence that ethnicity of the adolescent and the sex of the examining physician may contribute significantly to the success of the health care interaction.

HIV infection: a retrospective analysis of adolescent high-risk behaviors.

INTRODUCTION: The purpose of this study was to retrospectively ascertain behaviors and activities that may constitute high risk during the adolescent years (ages 12-18) of young adults (ages 20-25) who are infected with human immunodeficiency virus (HIV). METHODS: Subjects (n = 44) from 1 of 5 clinics in a large midwestern city completed a survey form, developed by the investigators, which examined 6 areas of behavior and activities that the literature suggested may be associated with high-risk behaviors. RESULTS: The adolescent high-risk profile of an HIV-infected young man includes sexual abuse before the age of 12 years, heavy consumption of alcohol, heavy consumption of a variety of illicit drugs, a wide variety of sexual experiences at very young ages, and multiple sexual partners. The adolescent high-risk profile of an HIV-infected young woman in this study includes heavy consumption of alcohol, heavy consumption of a variety of illicit drugs, and unprotected vaginal intercourse at very young ages as evidenced by a high number of sexually transmitted diseases at very young ages. DISCUSSION: Although the small number of participants in this study restricts interpretation of the results, adolescent health initiatives should be examined in light of these findings. Programs and services must consider the context of psychosocial situations, as well as past experiences, and incorporate this knowledge into prevention strategies.

The emergency medical response to the Cantara hazardous materials incident.

On 14 July 1991, at 2150 h, a train derailment occurred near the Cantara rail curve about six miles above Dunsmuir in Northern California. The derailment spilled approximately 19,000 gallons of metam-sodium into the Sacramento River. When mixed with water, metam-sodium degrades to methylisothiocyanate (MITC) and other gases. The contaminated river water passed the town of Dunsmuir and other occupied areas exposing residents to MITC gas. From 15 July to 20 July (five days), a total of 360 people underwent triage. The majority of patients displayed minor exposure symptoms that did not require hospital care. Mercy Mt. Shasta Hospital, a small rural hospital close to Dunsmuir, received the majority of patients. As of 29 July, 15 days after the incident, Mercy Mt. Shasta Hospital had seen 244 exposed patients in its emergency department, and had admitted five. Three had symptoms that could have been spill-related. Three Regional Poison Control Centers provided medical toxicology advice. Medical management of the emergency medical services (EMS) response to the event was piecemeal and weak. There did not appear to be a medical operations component at local Emergency Operations Centers (EOC). Most health care personnel interviewed complained about inadequate information about the substance and the situation. Local fire service mutual-aid agreements to obtain additional fire service and ambulance personnel worked well. It is important to emphasize that everyone who believed they had been exposed to the chemical underwent triage and received appropriate acute medical care.