Establishment of an in vitro assay to measure the invasion of ovarian carcinoma cells through mesothelial cell monolayers

Ovarian carcinoma is the leading cause of gynecological cancer deaths in the United States. Secondary tumor growths form by tumor cell invasion through the mesothelial lining of the peritoneal cavity and peritoneal organs. To study this interaction, we developed a dye-based in vitro model system in which mesothelial cells were grown as confluent monolayers, permeabilized, and then co-cultured with ovarian carcinoma cells for up to seven days. The mesothelial cells were then stained with trypan blue dye, which enabled the visualization of ovarian carcinoma cell invasion through the monolayers of mesothelial cells. Ovarian carcinoma cell invasion was inhibited for up to 7 days by the addition of GRGDSP peptides, a blocking monoclonal antibody against the β1 integrin subunit, or blocking monoclonal antibodies against matrix metalloproteinases 2 and 9. Cell invasion was also inhibited by hyaluronan and GM6001, a chemical inhibitor of matrix metalloproteinases. Differential gene expression of matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and disintegrins were observed in primary ovarian carcinoma tumors and secondary metastases, compared to normal ovaries. Taken together, these results suggest that complex interactions between integrins, disintegrins, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinases may mediate ovarian carcinoma cell invasion, and that the dye-based assay described herein is a suitable model system for its study. This revised version was published online in July 2006 with corrections to the Cover Date.     

Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.     

Development of a sensitive PCR-dot blot assay to supplement serological tests for diagnosing Lyme disease

Laboratory diagnosis of Lyme disease is difficult and presently dependent on detecting Borrelia burgdorferi-specific antibodies in patient serum with the disadvantage that the immune response to B. burgdorferi can be weak or variable, or alternatively, the slow and inefficient culture confirmation of B. burgdorferi. PCR tests have previously shown poor sensitivity and are not routinely used for diagnosis. We developed a sensitive and specific Lyme Multiplex PCR-dot blot assay (LM-PCR assay) applicable to blood and urine samples to supplement western blot (WB) serological tests for detecting B. burgdorferi infection. The LM-PCR assay utilizes specific DNA hybridization to purify B. burgdorferi DNA followed by PCR amplification of flagellin and OspA gene fragments and their detection by southern dot blots. Results of the assay on 107 and 402 clinical samples from patients with suspected Lyme disease from Houston, Texas or received at the IGeneX laboratory in Palo Alto, California, respectively, were analyzed together with WB findings. The LM-PCR assay was highly specific for B. burgdorferi. In the Texas samples, 23 (21.5%) patients antibody-negative in WB assays by current US Centers for Disease Control (CDC) recommended criteria were positive by LM-PCR performed on urine, serum or whole blood samples. With IGeneX samples, of the 402 LM-PCR positive blood samples, only 70 met the CDC criteria for positive WBs, while 236 met IGeneX criteria for positive WB. Use of the LM-PCR assay and optimization of current CDC serological criteria can improve the diagnosis of Lyme disease.     

The complicated ‘Yes’: Decision-making processes and receptivity to lung cancer screening among head and neck cancer survivors

Objective

Shared decision making (SDM) is recommended when offering lung cancer screening (LCS)—which presents challenges with tobacco-related cancer survivors because they were excluded from clinical trials. Our objective was to characterize head and neck cancer (HNC) survivors’ knowledge, attitudes, and beliefs toward LCS and SDM.

Intensive referral to mutual-help groups: A field trial of adaptations for rural veterans

Objective

A multisite field trial testing whether improved outcomes associated with intensive referral to mutual help groups (MHGs) could be maintained after the intervention was adapted for the circumstances and needs of rural veterans in treatment for substance use disorder (SUD).

Keeping the patient in the center: Common challenges in the practice of shared decision making

Objective

To examine situations where shared decision making (SDM) in practice does not achieve the goal of a patient-centered decision.

Association between maternal depression and maternal sensitivity from birth to 12 months: a meta-analysis

Maternal sensitivity plays a central role in shaping children’s development across a number of domains, and may be disrupted by depression. The current meta-analysis quantified the magnitude of the association between depression and maternal sensitivity, defined broadly as timely, contingent, and appropriate responding to infants’ cues, from birth to 12 months. Across k = 48 studies and n = 4,934 mother–infant dyads, the aggregate effect size between depression and maternal sensitivity was r = ?.16, p < .0001, indicating that mothers with higher depression levels were less sensitive than mothers with lower depression levels. Studies that compared a depressed group with a nondepressed/control group had larger effect sizes (r = ?.35, p < .0001) than studies that examined depression within a single sample of either unselected cases or clinical-only cases (r = ?.11, p < .001), suggesting that clinical levels of depression may pose a particular threat to sensitive parenting. Clinical implications (e.g. screening, prevention) are discussed.     

Impact of payer status on treatment of cervical cancer at a tertiary referral center

Objectives

The study aims to determine the impact of payer status on the likelihood of receiving definitive treatment for invasive cervical cancer at a tertiary medical center.

Methods

All consecutive patients presenting to Johns Hopkins Hospital with a diagnosis of invasive cervical cancer between 1/1/95-12/31/08 were retrospectively identified from the tumor registry. Demographic and clinical information were abstracted from the medical record. Payer status was categorized as private, public, no insurance, or unknown. Treatment was defined as surgery, chemo-radiation, chemotherapy, radiation, or no definitive therapy. The likelihood of receiving no definitive therapy was analyzed using Pearson chi-square analysis, univariate and multivariate models.

Results

A total of 306 patients were identified. Median age was 47 and 60% of patients had early stage disease at diagnosis (stages IA-IIA). Fifty-six percent of the cohort had private insurance, 34% had public insurance, and 6% had no insurance. Having no insurance was the single most significant risk factor associated with receiving no standard therapy. While 7% of privately insured and 4% of publicly insured patients did not receive definitive therapy, 16% of uninsured patients did not receive definitive treatment. In multivariate analysis controlling for age, race, stage, histology, and comorbidities, uninsured payer status was a significant and independent predictor of receiving no definitive treatment (OR 8.01, CI 1.265-50.694, p = 0.027) than patients with public insurance.

Conclusions

In this study, uninsured payer status was significantly associated with a higher likelihood of not receiving standard therapy for cervical cancer. Additional studies are warranted to characterize specific barriers to care for this at-risk population.