Antiangiogenic gene therapy of cancer: recent developments

With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. Gene therapy represents an attractive alternative to recombinant protein administration for several reasons. This review evaluates the potential advantages of gene transfer for antiangiogenic cancer therapy and describes preclinical gene transfer work with endogenous angiogenesis inhibitors demonstrating the feasibility of effectively suppressing and even eradicating tumors in animal models. Additionally, we describe the advantages and disadvantages of currently available gene transfer vectors and update novel developments in this field. In conclusion, gene therapy holds great promise in advancing antiangiogenesis as an effective cancer therapy and will undoubtedly be evaluated in human clinical trials in the near future

Is there a role for sentinel lymph node biopsy in the management of sarcoma?

A review of the role for sentinel lymph node biopsy in sarcoma.Is there a role for sentinel lymph node (SLN) biopsy in the management of sarcoma? Sentinel node biopsy has dramatically changed the management of melanoma and breast cancer, helping surgeons avoid radical lymphadenectomies in node negative patients who would previously have undergone a more morbid operation with little benefit, or remained pathologically unstaged. Many investigators have explored the use of lymphatic mapping for malignancies other than breast cancer or melanoma. Lymphatic mapping and sentinel node biopsy has not been investigated in the management of sarcomas, which is not surprising given that the majority of sarcomas spread by local extension or hematogenously. Regional lymph node metastases are rare; developing in about 3–10% of patients with localized disease. However, among certain subtypes of high-grade sarcomas there is a propensity for regional lymph node metastases. These include rhabdomyosarcoma, epithelioid sarcoma, clear cell sarcoma, synovial sarcoma, and vascular sarcomas. It is in these particular subtypes that there may be a benefit to SLN biopsy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/39196/1/sarcoma SLN.pd

Surgical Therapy of Cutaneous Melanoma

For most solid tumors, therapy has evolved from surgery alone to a multidisciplinary approach. Malignant melanoma remains an exception, with surgery maintaining the principal role not only for treatment of the primary lesion but also staging and the management of advanced disease. The surgical management of melanoma has evolved over the years, resulting in a substantial decrease in the morbidity associated with treatment wihtout a compromise in outcome. This article will review the changes that have occured leading to the current surgical approach to melanoma, the evidence behind these recommendations, and new questions that need to be addressed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/51541/1/Surgical Therapy of Cutaneous Melanoma.pd

Sex and depression in the National Comorbidity Survey I: Lifetime prevalence, chronicity and recurrence

Basic epidemiologic prevalence data are presented on sex differences in DSM-III-R major depressive episodes (MDE). The data come from the National Comorbidity Survey (NCS), the first survey in the U.S. to administer a structured psychiatric interview to a nationally representative sample of the general population. Consistent with previous research, women are approximately 1.7 times as likely as men to report a lifetime history of MDE. Age of onset analysis shows that this sex difference begins in early adolescence and persists through the mid-50s. Women also have a much higher rate of 12-month depression than men. However, women with a history of depression do not differ from men with a history of depression in either the probability of being chronically depressed in the past year or in the probability of having an acute recurrence in the past year. This means that the higher prevalence of 12-month depression among women than men is largely due to women having a higher risk of first onset. The implications of these results for future research are discussed in a closing section of the paper.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30529/1/0000161.pd

Sex and depression in the national comorbidity survey. II: Cohort effects

Data from a nationally representative sample of the general population are used to study cohort differences in the prevalence of DSM-III-R Major Depressive Episode (MDE). We document increasing lifetime prevalence of MDE among both men and women in more recent cohorts, but no major change in the sex ratio over the 40-year period retrospectively covered in the survey. We find a cohort a cohort difference in 12-month MDE, with older women much more likely than older men to have recurrent episodes. This sex difference in recurrence plays an important part in the elevated 12-month prevalence of depression among women compared to men in the 45-54 age range.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31852/1/0000801.pd

A dimensional approach to understanding severity estimates and risk correlates of marijuana abuse and dependence in adults: A dimensional approach to marijuana use disorders

While item response theory (IRT) research shows a latent severity trait underlying response patterns of substance abuse and dependence symptoms, little is known about IRT-based severity estimates in relation to clinically relevant measures. In response to increased prevalences of marijuana-related treatment admissions, an elevated level of marijuana potency, and the debate on medical marijuana use, we applied dimensional approaches to understand IRT-based severity estimates for marijuana use disorders (MUDs) and their correlates while simultaneously considering gender- and race/ethnicity-related differential item functioning (DIF). Using adult data from the 2008 National Survey on Drug Use and Health (N=37,897), DSM-IV criteria for MUDs among past-year marijuana users were examined by IRT, logistic regression, and multiple indicators–multiple causes (MIMIC) approaches. Among 6,917 marijuana users, 15% met criteria for a MUD; another 24% exhibited subthreshold dependence. Abuse criteria were highly correlated with dependence criteria (correlation=0.90), indicating unidimensionality; item information curves revealed redundancy in multiple criteria. MIMIC analyses showed that MUD criteria were positively associated with weekly marijuana use, early marijuana use, other substance use disorders, substance abuse treatment, and serious psychological distress. African Americans and Hispanics showed higher levels of MUDs than whites, even after adjusting for race/ethnicity-related DIF. The redundancy in multiple criteria suggests an opportunity to improve efficiency in measuring symptom-level manifestations by removing low-informative criteria. Elevated rates of MUDs among African Americans and Hispanics require research to elucidate risk factors and improve assessments of MUDs for different racial/ethnic groups

Use of item response theory and latent class analysis to link poly-substance use disorders with addiction severity, HIV risk, and quality of life among opioid-dependent patients in the Clinical Trials Network

This study applied item response theory (IRT) and latent class analysis (LCA) procedures to examine the dimensionality and heterogeneity of comorbid substance use disorders (SUDs) and explored their utility for standard clinical assessments, including the Addiction Severity Index (ASI), HIV Risk Behavior Scale (HRBS), and SF-36 quality-of-life measures