Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.     

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Heparin octasaccharides inhibit angiogenesis in vivo.

BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.     

Determination of the pericardial to serum myoglobin ratio for the early diagnosis of perioperative myocardial infarction after coronary artery bypass grafting.

Pericardial fluid reflect the composition of cardiac interstitium in myocardial ischemia. This study investigated the value of the pericardial and serum myoglobin (MG) measurements for the diagnosis of perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG). Postoperative arterial and pericardial blood samples were taken in 64 subjects undergoing elective CABG allocated to two groups according to the 12-lead electrocardiogram (ECG) abnormalities observed during the first postoperative 24h. Group 1=normal and nonspecific ECG abnormalities, and Group 2=perioperative Q-wave MI. The occurrence of perioperative MI was associated with a dramatic increase in both serum and pericardial cardiac troponin I (CTnI) and MG concentrations. Pericardial concentrations were higher than serum concentrations during the first postoperative 24h in all subject. However, pericardial/serum CTnI ratio in subjects in Group 2 was not statistically different from Group 1 at the time of admission to the intensive care unit (ICU) and did not significantly change at time intervals. On the other hand, more than two-fold increase in the pericardial/serum MG ratio was determined for all patients who experienced perioperative Q-wave MI with the lowest value as 2.75, whereas only 1 of 59 patients in group 1 had the ratio higher than 2 with the highest value as 2.15 at the time of admission to the ICU. In conclusion, determination of pericardial/serum MG ratio may be a useful tool for the early diagnosis of the perioperative MI after CABG.     

Mother's dietary diversity and association with stunting among children <2 years old in a low socio‐economic environment: A case–control study in an urban care setting in Dhaka,Bangladesh

Mothers are often responsible for preparing nutritious foods in their households. However, the quality of mother's diets is often neglected, which may affect both mother's and child's nutrition. Because no single food contains all necessary nutrients, diversity in dietary sources is needed to ensure a quality diet. We aimed to study the association between mother's dietary diversity and stunting in children <2 years attending Dhaka Hospital of icddr,b, a diarrhoeal disease hospital in Dhaka, Bangladesh. A case–control study (n = 296) was conducted from November 2016 to February 2017. Data were collected from mothers of stunted children <2 years (length‐for‐age z score [LAZ] < ?2) as “cases” and nonstunted (LAZ ≥ ?1) children <2 years as “controls.” Mothers were asked to recall consumption of 10 defined food groups 24 hr prior to the interview as per Guidelines for Minimum Dietary Diversity for Women. Among the mothers of cases, 58% consumed <5 food groups during the last 24 hr, compared with 45% in control mothers (P = 0.03). Children whose mothers consumed <5 food groups were 1.7 times more likely to be stunted than children whose mothers consumed ≥5 food groups (P = 0.04). Intake of food groups such as pulses, dairy, eggs, and vitamin A rich fruit was higher in control mothers. Proportion of mother's illiteracy, short stature, monthly family income <BDT 11,480, absence of bank account, and poor sanitation was also found to be higher in stunted group. Further study particularly intervention or longitudinal study to see the causality of mother's dietary diversity with child stunting is recommended.     

Real-world effectiveness of BNT162b2 mRNA vaccine: a meta-analysis of large observational studies

Inflammopharmacology - This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search...     

The risk of mortality in patients with COVID-19 with pre-diagnosis use of NSAIDs: a meta-analysis

Inflammopharmacology - The notion that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may lead to adverse outcomes upon acquisition of coronavirus disease 2019 (COVID-19) should be...