Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

IntroductionTryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer.MethodsDynamic α-[¹¹C]methyl-l-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens.ResultsTumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells.ConclusionsBreast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.     

Neonatal hydrocephalus in the offspring of rats fed during pregnancy non-toxic amounts of tellurium

Summary Because of the consistency with which a rapidly progressing hydrocephalus internus can be produced in the offspring of rats fed on a diet containing tellurium during pregnancy, this heavy metal appears to be an easy to handle and promising tool for the investigation of certain aspects of the congenital non-obstructive hydrocephalus internus.

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Zusammenfassung Nachkommen von Ratten, die während der Tragzeit mit geringen, kaum toxisch wirkenden Mengen von Tellur gefüttert wurden, entwickelten einen rasch progredienten Hydrocephalus internus. Tellur erscheint daher als einfaches und vielversprechendes Mittel zur Untersuchung kongenitaler nicht obstruktiver Hydrocephalus-Syndrome.

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Dedicated toWillibald Scholz, Munich, on the occasion of his 75th birthday.

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This investigation was supported by a Research Grant NB-02275 from the National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Md.     

Anti-xanthine oxidase antibodies in sera and synovial fluid of patients with rheumatoid arthritis and other joint inflammations

OBJECTIVE: To study anti-bovine milk xanthine oxidoreductase XOR antibody levels in synovial fluid as well as in serum of patients suffering from rheumatoid affections to assess a possible correlation between antibody titres and severity of disease. METHODS: Sera and synovial fluids were collected from volunteer donors at Setif University Hospital, Setif, Algeria from 2001--2007 with the consent of patients. Human IgG and IgM levels of free and bound anti-bovine milk XOR antibodies were determined using bovine XOR as antigen, with enzyme-linked immunosorbent assay ELISA. RESULTS: Serum IgG anti-bovine milk XOR titres in 30 healthy normal subjects 2.74+/-2.31 microgram/mL are in agreement with that reported in the literature. Immunoglobulin G and IgM anti-bovine milk XOR antibody titres were found to be significantly higher in serum from patients with rheumatoid arthritis RA, and latex positives subjects. Synovial IgM antibody titres to bovine XOR were found to be significantly higher in rheumatoid arthritis patients compared to patients with other joint inflammations. CONCLUSION: In rheumatoid arthritis patients, high concentrations of antibodies against XOR were noticed. These antibodies may play a major role in RA by inhibiting both xanthine and NADH oxidase activities of XOR. They may also play a key role in eliminating XOR from serum and synovial fluid positive role but unfortunately, immune complex formation could also activate complement and participate in self maintenance of inflammation.     

Racial disparities in Human Papillomavirus (HPV) associated head and neck cancer

Purpose

Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use.

Materials and methods

385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients’ demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox’s proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV-positivity, respectively.

Results

HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05–0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42–4.59) decreased to almost unity (HR 1.49, 95% CI 0.75–2.93) after adjustment for HPV and smoking.

Conclusions

Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC.     

Medicaid Covered Births, 2008 Through 2010, in the Context of the Implementation of Health Reform

BackgroundMedicaid is a major source of public health care financing for pregnant women and deliveries in the United States. Starting in 2014, some states will extend Medicaid to thousands of previously uninsured, low-income women. Given this changing landscape, it is important to have a baseline of current levels of Medicaid financing for births in each state. This article aims to 1) provide up-to-date, multiyear data for all states, the District of Columbia, and Puerto Rico and 2) summarize issues of data comparability in view of increased interest in program performance and impact assessment.MethodsWe collected 2008–2010 data on Medicaid births from individual state contacts during the winter of 2012–2013, systematically documenting sources and challenges.FindingsIn 2010, Medicaid financed 48% of all births, an increase of 19% in the proportion of all births covered by Medicaid in 2008. Percentages varied among states. Numerous data challenges were found.Conclusions/Implications for Research and PolicyConsistent adoption of the 2003 birth certificate in all states would allow the National Center for Health Statistics Natality Detail dataset to serve as a nationally representative source of data for the financing of births in the United States. As states expand coverage to low-income women, women of childbearing age will be able to obtain coverage before and between pregnancies, allowing for access to services that could improve their overall and reproductive health, as well as birth outcomes. Improved birth outcomes could translate into substantial cost savings, because the costs associated with preterm births are estimated to be 10 times greater than those for full-term births.     

Coping patterns in Latino families of children with asthma

Introduction

Using the Coping Health Inventory for Parents (CHIP), this study examined coping behaviors in 26 Latino parents of children with asthma.

Methods

Correlations and t tests were used to look at variables related to the parents' coping patterns and to compare their frequency of usage of these patterns.

Results

The parents in this study were most likely to cope with their child's asthma by making active attempts to understand this condition, doing activities with family members, and maintaining an optimistic perspective. Child and family variables were not significantly associated with parents' usage of coping patterns.

Discussion

These results shed light on coping in Latino families of children with asthma and contribute to a growing framework of research and practice regarding health problems in this population. The aforementioned results can enhance health care professionals' understanding of the experiences of these families and help develop and expand culturally sensitive interventions to positively affect their health and psychological needs.     

Dietary energy balance modulates ovarian cancer progression and metastasis

A high energy balance, or caloric excess, accounts as a tumor promoting factor, while a negative energy balance via caloric restriction, has been shown to delay cancer progression. The effect of energy balance on ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8 cancer cells. Tumor evaluation revealed that mice group on HED displayed the most extensive tumor formation with the highest tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of insulin, leptin, insulin growth factor-1 (IGF-1), monocyte chemoattractant protein-1 (MCP-1), VEGF and interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least tumor burden associated with a significant reduction in levels of insulin, IGF-1, leptin, MCP-1, VEGF and IL-6. Immunohistochemistry analysis of tumors from HED mice showed higher activation of Akt and mTOR with decreased adenosine monophosphate activated kinase (AMPK) and SIRT1 activation, while tumors from the CRD group exhibited the reverse profile. In conclusion, ovarian cancer growth and metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of growth factors, cytokines and altered regulation of AMPK and SIRT1 that converges on mTOR inhibition. While the role of a high energy state in ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer therapies and as possible individualized treatment strategy of epithelial ovarian cancer.