Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications

The in vitro and in vivo characterization of adult stem cells has allowed researchers to identify certain specific functional features to each tissue-specific stem cell. Moreover, recent studies revealed that their malignant counterparts, the cancer progenitor cells with stem cell-like properties, may assume a crucial role for the initiation and progression of locally invasive cancers into disseminated and incurable disease states. Therefore, a new direction in cancer research appears necessary in considering the critical functions of cancer progenitor cells. In this review, we discuss recent concepts on the critical roles of tumorigenic and migrating cancer progenitor cells in carcinogenesis. Particularly, we describe the tumorigenic cascades that are frequently activated through the interplay of diverse hormones, growth factors, cytokines and integrins in cancer progenitor cells versus their further differentiated progeny. The emphasis is on the oncogenic signaling pathways activated during the localized cancer progression and micrometastatic events involved in tumor formation at distant sites such as bone marrow. Of therapeutic interest, important information for the selective molecular targeting of cancer progenitor cells, which must now be considered in developing new effective diagnostic and prognostic methods and curative treatments against the most locally advanced and metastatic cancers, is also described.     

Four‐year allograft survival in a highly sensitized combined liver–kidney transplant patient despite unsuccessful anti‐HLA antibody reduction with rituximab,splenectomy, and bortezomib

Although donor‐specific lymphocytotoxic antibodies are regarded as a contraindication for kidney transplantation (KTx), the data available for liver or combined liver or kidney transplantation (cLKTx) are scarce. Here, we report a case of a highly sensitized young man receiving his sixth liver and second kidney graft. Multiple anti‐HLA antibodies were present at the time of transplantation. As a result of suspected antibody‐mediated graft damage, the patient was treated with rituximab, plasmapheresis, intravenous immunoglobulins, splenectomy, and bortezomib to decrease the antibody production. So far, patient and allograft survival has reached 4 years despite failure to achieve a permanent reduction of anti‐HLA antibodies, and particularly nondonor directed antibodies.     

Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases

A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur.
We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudoepitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.     

Fish oil supplementation does not alter energy efficiency in healthy males

BACKGROUND AND AIMS: Fish oil (FO) supplementation prevents the development of obesity and insulin resistance, and upregulate the expression of UCP3 in skeletal muscle in rodents. This may represent indirect evidence that FO promotes fat oxidation and/or alter energy efficiency. The aim of this study was to evaluate whether such effects can be observed in humans. The metabolic effects of FO were assessed during exercise in order to obtain a direct measurement of energy efficiency. METHODS: Eight healthy male volunteers were studied with and without supplementation with 7.2 g/day FO (including 1.1 g/day eicosopentaenoic acid and 0.7 g/day decosahexaenoic acid) during 14 days. Their VO(2 max) was measured on cycle ergometer. Thereafter, energy metabolism (substrate oxidation, energy expenditure and energy efficiency) was assessed during a 30 min cycling exercise at 50% VO(2 max) performed 2 h 30 after a standardized, high carbohydrate breakfast. RESULTS: VO(2 max) was 38.6+/-2.2 after FO and 38.4+/-2.0 (mL x kg(-1) x min(-1)) in control conditions (NS). Basal plasma glucose, insulin and NEFA concentrations, and energy metabolism were similar with FO and in controls. During exercise, the increases in plasma NEFA concentrations, energy expenditure, glucose and lipid oxidation, and the decreases in glycaemia and insulinemia were not altered by FO intake. Energy efficiency was 22.4+/-0.6% after FO vs 21.8+/-0.7% in controls. In order to ascertain that the absence of effects of FO was not due to consumption of a carbohydrate meal immediately before exercise, 4 of the 8 subjects were re-studied in fasting conditions, FO also failed to alter energy efficiency in this subset of studies. CONCLUSION: FO supplementation did not significantly alter energy metabolism and energy efficiency during exercise in healthy humans.     

Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in decreasing blood pressure in African patients is controversial. OBJECTIVE: We examined the ambulatory blood pressure (ABP) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy. DESIGN: A single-blind randomized AB/BA crossover design. SETTING: Hypertensive families of East African descent from the general population in the Seychelles. PARTICIPANTS: Fifty-two (29 men and 23 women) out of 62 eligible hypertensive patients were included.Main outcome measures ABP response to 20 mg lisinopril (LIS) daily and 25 mg hydrochlorothiazide (HCT) daily given for a 4-week period.Results The daytime systolic/diastolic ABP response to HCT was 4.9 [95% confidence interval (CI) 1.2-8.6]/3.6 (1.0-6.2) mmHg for men and 12.9 (9.2-16.6)/6.3 (3.7-8.8) mmHg for women. With LIS the response was 18.8 (15.0-22.5)/14.6 (12.0-17.1) mmHg for men and 12.4 (8.7-16.2)/7.7 (5.1-10.2) mmHg for women. The night-time systolic/diastolic response to HCT was 5.0 (0.6-9.4)/2.7 [(-0.4)-5.7] mmHg for men and 11.5 (7.1-16.0)/5.7 (2.6-8.8) mmHg for women, and to LIS was 18.7 (14.2-22.1)/15.4 (12.4-18.5) mmHg for men and 3.5 [(-1.0)-7.9]/2.3 [(-0.8)-5.4] mmHg for women. Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS. CONCLUSIONS: Hypertensive patients of African descent responded better to LIS than to HCT. Men responded better to LIS than to HCT and women responded similarly to both drugs.     

Prevalence of Low Bone Mineral Density in Men and Women Infected With Human Immunodeficiency Virus 1 and a Proposal for Screening Strategy

We analyzed data collected during screening for eligibility in the ANRS-120 FOSIVIR clinical trial to estimate the prevalence of osteoporosis in patients infected with human immunodeficiency virus 1 (HIV-1), to study its risk factors, and to develop a screening strategy. McNemar test was used to compare the estimated prevalence of osteoporosis, using 3 different definitions. We then derived a screening strategy for HIV-infected men.We analyzed data for 700 men and 192 women. The prevalence of osteoporosis differed markedly according to the definition used. Based on the “T-score ≤ ?2.5” definition, 14.9% of men and 1.0% of women had osteoporosis. Factors associated with low bone mineral density comprised not only classical risk factors for osteoporosis such as low body mass index (BMI) or older age but also factors associated with HIV infection such as lower CD4 T-cell nadir in men and AIDS in women, and with antiretroviral treatment such as recent tenofovir therapy.In addition to postmenopausal women, we recommend osteoporosis screening for HIV-infected men older than 60 yr, men younger than 60 yr with BMI <20 kg/m², and men younger than 60 yr with both BMI 20–23 kg/m² and a CD4 T-cell nadir ≤200/mm³.     

The local burden of emotional disorders. An analysis based on a large health survey in Catalonia (Spain)

Objective

Mental health conditions are associated with a significant burden on individuals. Using data from a large population health survey, the present study aimed to quantify the burden of emotional disorders (depression and anxiety) on health-related quality of life (HRQoL) in the region of Catalonia (Spain) for evidence-informed policy making.

Methods

Regression models were used to estimate the impact of emotional disorders on HRQoL, controlling by socioeconomic factors and somatic health problems. The rate of emotional disorders was based on the General Health Questionnaire (GHQ-12) and quality of life scores were based on the EQ-5D.

Results

The impact of emotional disorders on HRQoL was equal to a reduction of 0.17 in the EQ-5D score. Translation of this individual impact to population figures yielded a total loss of 78,742 quality-adjusted life years (QALYs) for 2006. This strong impact highlights the need for global policies aiming to reduce this burden.

Conclusion

The negative relation between emotional disorders and the HRQoL of individuals was confirmed and quantified for the population of Catalonia. The use of quality of life scales such as the SF or EQ-5D, combined with data on quasi-specific health conditions provides substantial information for prioritizing and planning health programs.     

Heritability and intrafamilial aggregation of arterial characteristics

BACKGROUND: We investigated the heritability and familial aggregation of various indexes of arterial stiffness and wave reflection and we partitioned the phenotypic correlation between these traits into shared genetic and environmental components. METHODS: Using a family-based population sample, we recruited 204 parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the Czech Republic (50). We measured peripheral pulse pressure (PPp) sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs) by applanation tonometry at the radial artery; and aortic pulse wave velocity (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively. RESULTS: We found significant heritability for PAIx, CAIx, PPc and mean arterial pressure ranging from 0.37 to 0.41; P < or = 0.0001. The method of intrafamilial concordance confirmed these results; intrafamilial correlation coefficients were significant for all arterial indexes (r > or = 0.12; P < or = 0.02) with the exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic correlation between PWV and the other arterial indexes were significant (rhoG > or = 0.29; P < 0.0001). The corresponding environmental correlations were only significantly positive for PPp (rhoE = 0.10, P = 0.03). CONCLUSION: The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits.     

Impact of age and gender on in-hospital and late mortality after acute myocardial infarction: increased early risk in younger women: results from the French nation-wide USIC registries.

AIMS: To determine whether sex differences of in-hospital and after-discharge mortality differ according to the age. METHODS AND RESULTS: Data of 4347 consecutive patients hospitalized within 48 h of the onset of acute myocardial infarction (AMI) were analysed. Patients were classified according to median age (68 years): Group 1 (G1) (308 women, 30-67 years), G2 (1878 men, 30-67 years), G3 (860 women, 68-89 years), and G4 (1301 men, 68-89 years). In both age groups, women were older, had more frequent co-morbidities, lower rate of reperfusion therapy, and received less anti-platelet agents, beta-blockers, and statins than men. The overall 1-year mortality was higher in women (25% vs. 16% in men, P<0.0001). After adjustment, in-hospital mortality was higher only for the women in the younger age group. (G1 vs. G2: OR=2.2, 95%CI=1.3-3.8; G3 vs. G4: OR=1.1, 95%CI=the risk of death, after hospital discharge, was no longer related to gender in any age group. CONCLUSION: The higher 1-year mortality following AMI in women is explained by the higher risk of death in young women during the first days of hospitalization. Further investigations are crucial to determine the cause in order to improve the chance of survival in younger women.