Relevance of tumor microenvironment for progression, therapy and drug development

Tumor interstitium exhibits a microenvironment that differs from corresponding normal tissues. Tumor phenotype shows, for example, an elevated intracellular pH (pHi), a lowered extracellular pH (pHe), a low oxygen concentration and low glucose levels. These differences are caused by cell biological (so called intrinsic) factors, e.g. a higher acidification rate, as well as by more systemic (extrinsic) factors, e.g. poor tumor vascularization. They represent important factors for invasiveness, immune suppression and proliferation, and they imply possibilities for diagnosis, prognosis and therapy. We have developed an experimental data-based computer model, which has simulated the potential role of metabolic effects on tumor progression. We show an experiment on cellular metabolism demonstrating the immunosuppressive impact of low pHe on peripheral blood mononuclear cells. Finally, we review important findings on the tumor microenvironment leading to possibilities for therapy which are currently evolving and which promise higher effectiveness for cancer therapy.     

Medicaid managed care, substance abuse treatment, and people with disabilities: review of the literature

Most states enroll individuals with disabilities who receive Supplemental Security Income (SSI) in Medicaid managed care plans. The impact of managed care on these individuals, especially those with substance abuse disorders, is not well understood. A review of the literature related to substance abuse, disability, and Medicaid managed care suggests that substance abuse is a serious issue for individuals with disabilities. More research is needed to determine how the substance abuse treatment needs of individuals with disabilities can be met through Medicaid managed care. The authors identified topics for a research agenda on the needs of individuals with disabilities who also experience co-occurring substance abuse disorders. Implications for social work policy and practice are discussed.     

Change in cardiovascular risk factors in France, 1985–1997

The change in the main cardiovascular risk factors in France was assessed using the MONICA population surveys conducted in the Urban Community of Lille, Bas-Rhin and Haute-Garonne. Trends in obesity, tobacco smoking, hypertension, hypercholesterolaemia and self-reported diabetes were established for the first (1985-1988) and the last (1995-1997) survey. The results indicate that the prevalence of overweight and obesity remained stable in both genders; tobacco smoking decreased in men but increased in women. Prevalence of hypertension decreased, and preventive measures improved in both genders. Prevalence of hypercholesterolaemia remained stable, and preventive measures improved only in men. Prevalence of self-reported diabetes increased solely in women, and preventive measures improved in both genders. However, in 1995-1997 still 40% of the treated hypertensive and 30% of the treated hypercholesterolaemic subjects were not adequately controlled. We conclude that prevalence and prevention of the main cardiovascular risk factors have evolved favourably in France, but the management of hypercholesterolaemia and hypertension can still be improved.     

B-cell chronic lymphocytic leukemia with aberrant CD8 expression: genetic and immunophenotypic analysis of prognostic factors

B-cell chronic lymphocytic leukemia (B-CLL) is phenotypically characterized by cell surface co-expression of CD19, CD20, CD5, and CD23. However, the concomitant presence of other antigens distinctive of a particular leukocyte subset, e.g. T cells, is an unusual finding in B-CLL. In the present report, a case of B-CLL with aberrant expression of the T-cell-associated antigen CD8 is described. Flow cytometric analysis of the patient's cells demonstrated lack of CD38 expression, and cytogenetic analysis by FISH did not show any abnormalities of chromosomes 17p, 11q, and 12. Furthermore, the B-CLL cells expressed only low levels of the tyrosine kinase ZAP-70, which was in agreement with the mutated status of the immunoglobulin heavy-chain variable-region gene (IgVH). In summary, the determined profile of prognostic markers together with the highly stable and indolent disease in the described patient suggest a good prognosis of B-CLL with aberrant CD8 expression.     

Peripheral blood-derived bovine dendritic cells promote IgG1-restricted B cell responses in vitro

Regulation of humoral responses involves multiple cell types including the requirements for cognate interactions between T and B cells to drive CD40-dependent responses to T-dependent antigens. A third cell type has also been shown to play an essential role, the dendritic cell (DC). We demonstrate that bovine peripheral blood-derived (PB)-DC are similar in function to features described for human interstitial DC including the production of signature type 2 cytokines [interleukin (IL)-13, IL-10]. PB-DC express moderate-to-high costimulatory molecule expression, and major histocompatibility complex class II is negative for CD14 expression and has low or no expression of CD11c. Consistent with the interstitial phenotype is the ability of PB-DC to influence B cell activation and differentiation via direct expression of CD40L and type 2 cytokines. Collectively, these results suggest that direct B cell-DC interactions may promote an immunoglobulin-isotype expression pattern consistent with type 2 responses, independent of direct T cell involvement.     

Further delineation of Raine syndrome

We report o a baby from an Arab family with Raine syndrome. The baby presented at birth with severe craniofacial anomalies including a wide anterior fontanelle, exophthalmos, severe depression of the nasal bridge with a hypoplastic midface, bilateral choanal atresia and a large protruding tongue. All the limbs were short and the thorax was small. Radiologically there was increased bone density in some bones, periosteal new bone formation and marked bowing of the femurs, tibiae, and ulnae. We suggest that osteosclerosis in Raine syndrome is not necessarily severe and generalized, and bowing of the long bones is another variable radiological feature of the syndrome.