Interaction of mouse prolactin with mouse hepatic receptors

Lactogenic receptors are usually studied in heterologous systems where prolactin is derived from one species and receptors prepared from another. In such systems the foreign prolactin could be seen as a growth hormone by the host tissue. We have therefore developed a homologous radioreceptor assay using secreted mouse prolactin (smPRL) and mouse hepatic receptors. In this system, monovalent anions augment the smPRL-receptor interaction in the order F- greater than Cl- greater than Br- greater than I-. Divalent cations (Mg2+, Ca2+, Sr2+), phosphate and acetate also increase smPRL binding. Temperature and pH optima are at 8 degrees C and pH 8.3, respectively. Under optimum conditions, the percent total, specific and nonspecific binding are 55%, 45% and 10%, respectively. At infinite receptor concentration the maximum specific bindability of labeled smPRL is 50%. The effects of ions on binding of smPRL to the receptor show that hydrophobic forces participate in smPRL-receptor coupling. The biphasic dissociation kinetics show initial and final rate constants of 1.56 X 10(-4)/s and 7.62 X 10(-6)/s, respectively. The lactogenic receptor does not bind mouse growth hormone; however, it binds both mouse placental lactogen (mPL) and smPRL with equilibrium association constants of 3.90 X 10(8) M-1 and 2.25 X 10(8) M-1, respectively, suggesting that smPRL and mPL share biological roles by acting through the same receptor.     

Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy

We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR) in 46 biopsy samples from patients with advanced head and neck cancer treated with induction combination chemotherapy of 5-fluorouracil, cisplatin, and paclitaxel. Tumour expression of p53 protein was analysed with the monoclonal D07 antibody and EGFR with monoclonal H11 antibody. The overall response, defined as complete (CR) and partial response (PR) rates to treatment, was 88%. p53 positive staining was significantly more frequent in patients who did not respond to the induction treatment. EGFR expression failed to show any correlation with the response rate. Multivariate analysis indicated that a tumour location in the oral cavity together with p53 expression combined with moderate-to-high EGFR staining were independent prognostic factors of a shorter disease-free survival (DFS). Location of the tumour in the oral cavity and EGFR expression had independent prognostic value for overall survival (OS). We conclude that the EGFR status and an oral cavity location of the tumour have independent prognostic value in patients with advanced head and neck carcinoma treated with induction chemotherapy. The p53 status appears to be a determinant of the tumour chemo-sensitivity in advanced head and neck squamous cell carcinoma (HNSCC). The presence in the tumour of a p53-positive stain and moderate-to-high staining of EGFR is associated with a shorter DFS and time to treatment failure (TTF) probably reflecting a more aggressive tumour phenotype.     

Importance of heterotrimeric G proteins in prostate cancer molecular biology

ObjectiveTo deep in the knowledge of the involvement of G-protein αs and αi subunits in human prostate cancer.MethodsProstate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein αs and αi subunits were studied for expression (mRNA by RT-PCR and protein by Western-blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations (analysis with restriction enzymes and cDNA sequentiation).ResultsAt mRNA level, the expression of αs, αi1, αi2 y αi3 was detected in healthy and cancerous tissues. At protein level, the expression of αs y αi1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of αi3/0 also diminished, whereas that of ß subunit was not modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the control. Digestion with restriction enzymes Eag I or AlwN I did not allow to locate mutations in αs. However, digestion at αi2 level with BstU I enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG).ConclusionsThe functionality and expression of heterotrimeric G proteins are selectively modified in human prostate adenocarcinoma, occurring in addition some punctual mutation. The observed substitution of Gln205 by Pro may result in a low GTPase activity for αi2 that, therefore, is stabilized in its active form.     

Short‐ and long‐term results of a programme for the prevention of readmissions and mortality in patients with heart failure: Are effects maintained after stopping the programme?

The objective of the study was to evaluate whether improvements obtained during an intervention programme were maintained after the programme was stopped. 153 patients discharged with a diagnosis of heart failure (HF) were randomized to either usual care or an intervention programme, which included patient education, consultation with the cardiologist and monitoring in the Heart Failure Unit. After an average period of 16+/-8 months, the intervention programme was stopped. One year later, all the patients were re-examined to assess HF readmissions, all-cause mortality, quality of life, and prescribed medical treatment. During the 16+/-8-month treatment period, patients in the intervention group had a lower rate of HF readmissions (17% vs. 51%, p<0.01), less all-cause mortality (13% vs. 27%, p=0.03), improvement in quality of life (1.5+/-0.8 vs. 1.9+/-1, p=0.03) and optimisation of medical treatment was achieved. One year after stopping the intervention, there was no difference in HF readmissions (28% vs. 25%, p=0.72), all-cause mortality (14% vs. 17%, p=0.64) and quality of life (1.7+/-0.9 vs. 1.8+/-1, p=0.24) between the groups. Survival and the probability of not being readmitted due to HF were similar in both groups. There was also a reduction in the use of beta-blockers and spironolactone in the intervention group. CONCLUSIONS: The positive effects of an intervention programme are clearly reduced when it is stopped, due to less strict control of the patients and a decrease in the use of drugs with proven efficacy in HF.