Immune checkpoint and angiogenic inhibitors for the treatment of hepatocellular carcinoma: It takes two to tangle.

Immunotherapy represents an effective and promising option in various cancers, including in hepatocellular carcinoma (HCC). The immune checkpoint inhibitors (ICIs) have shown a remarkable breakthrough in the last decade, in addition to molecular targeted therapy of angiogenesis such as tyrosine kinases inhibitors. ICIs provide new regimen that can be applied in different stages of the disease. In parallel, HCC progression is related to the tumor microenvironment (TME), involving the cross-talk between various cellular and non-cellular components within the TME niche. It appears logical to synergistically target several HCC components to increase the efficacy of the treatment. In this paper, we summarize evidence that the combination therapy of ICIs and angiogenesis inhibitors would be a potentially better strategy for HCC treatment.

The localization of PGE2 receptor subtypes in rat retinal cultures and the neuroprotective effect of the EP2 agonist butaprost.

It is concluded from immunohistochemical that all four types of prostaglandin-E(2) (PGE(2)) (EP1, EP2, EP3 and EP4) receptors are associated with specific cell-types in primary rat retinal cultures. Analysis specifically of EP2 receptor immunoreactivity shows it to coexist with some neurones expressing Thy-1 and calbindin immunoreactivities as well as with vimentin-positive Müller cells. Moreover, exposure of cultures to the EP2 specific agonist butaprost (100 nM) for a period of 24h results in a generation of cAMP thus providing support for the functionality of EP2 receptors. Cell survival was significantly affected in cultures where the serum concentration was reduced from 10 to 1% for 24h. This was reflected by a reduction in the number of GABA-positive neurons and an elevation of released lactate dehydrogenase (LDH) into the culture medium. Moreover, a number of cells displayed a clear generation of reactive oxygen species (ROS) and a staining for the breakdown of DNA by the TUNEL procedure as an indicator for apoptosis. These negative effects were attenuated when butaprost (100 nM) was present during the serum reduction and 30 min before the insult. The present studies provide evidence to show that all PGE(2) receptor types exist in the retina of rat pups, remain functional when the retinal cells are cultured and that specific activation of EP2 receptors with butaprost can attenuate a detrimental insult caused by insufficient serum that may occur in situ by reduced trophic support.

Physician gender and psychosocial care for children: attitudes, practice characteristics, identification, and treatment.

OBJECTIVE: To examine differences by physician gender in the identification and treatment of childhood psychosocial problems. DESIGN: Survey of patients (n = 19,963) and physicians (n = 366) in primary care offices in 2 large, practice-based research networks. Multivariate regressions were used to control for patient, physician, and visit characteristics, with a correction for the clustered sample. SUBJECTS: Children ages 4 to 15 years seen consecutively for nonemergent care. MEASURES: Physician report of attitudes, training, practice factors, and identification and treatment of psychosocial problems. Parental report of demographics and behavioral symptoms. RESULTS: Compared with male physicians, female physicians were less likely to view care for psychosocial problems as burdensome. They were more likely to see children who were female, younger, black or Hispanic, in single-parent households, enrolled in public or managed health plans, and with physical health limitations. Children seen by male physicians had higher symptom counts. Male physicians were more likely to report having primary care responsibility for their patient and that parents agree with their care plan. Female physicians spent more time with patients. After controlling for these differences, female physicians did not differ from male physicians in identification or treatment of childhood psychosocial problems. CONCLUSIONS: Male and female physicians see different kinds of children for different visit purposes and have different kinds of relationships with their patients. After controlling for these factors, management of childhood psychosocial problems does not differ by physician gender. Improving management of psychosocial conditions depends on identifying modifiable factors that affect diagnosis and treatment; our work suggests that characteristics of the practice environment, physician-patient relationship, and patient self-selection deserve more research.