Prognostic factors and survival in metastatic breast cancer: A single institution experience

Background

The current retrospective study aims to identify some determinants of survival in metastatic breast cancer.

Methods

The study concerned 332 patients with synchronous (SM) or metachronous (MM) metastatic breast cancer treated between January 2000 and December 2007. Statistical comparison between subgroups of patients concerning survival was carried out employing log-rank test for the invariable analysis and Cox model for the multivariable analysis. Factors included: age group (≤50 years vs. >50; ≤70 years vs. >70; ≤35 years vs. >35), menopausal status, presentation of metastatic disease (SM vs. MM), disease free interval (DFI) (≤24 months vs. >24 months; ≤60 months vs. >60 months), performance status at diagnosis of metastatic disease (PS) (0–1 vs. >1), hormone receptors (HR), number of metastatic sites (1 site vs. >1), nature of the metastatic site (visceral vs. non visceral), first line therapy, surgery of the primary tumor (SPT), locoregional radiotherapy (LRRT) and use or not of bisphosphonates.

Results

Overall survival at 5 years was 12%. Positive prognostic factors in univariate analysis were: age ≤ 70 years, hormono-dependence of the tumor, good PS (PS 0–1), less than two metastatic sites, no visceral metastases, DFI ≥ 24 months, SPT or LRRT. In multivariate analysis, favorable independent prognostic factors included: good PS (PS 0–1), absence of visceral metastases (liver, lung, brain) and age ≤ 70 years.

Conclusion

Many of the prognostic factors in metastatic breast cancer found in our study are known in the literature but some of them, like the application of locoregional treatment (radiotherapy or surgery) and the use of bisphosphonates, need to be further investigated in randomized clinical trials.     

Secreted recombinant P53 protein from Pichia pastoris is a useful antigen for detection of serum p53: autoantibody in patients with advanced colorectal adenocarcinoma

The detection of P53 alteration by serological method is easier to perform, does not require tumor tissues and is of interest for patients monitoring. In this study, we described the development of a home made ELISA test based on recombinant human P53 protein produced in Pichia pastoris and used as antigen for the detection of serum p53-Abs in colorectal carcinoma patients. The human P53 was secreted as a His-tagged protein by recombinant KM71 strain (Kα21) via the peptide signal α of the Saccharomyces cerevisiae mating type gene. The recombinant P53-His was able to detect p53-Abs in 23.4 % of patients. Serum p53-Abs correlated significantly with surgical treatment (P = 0.007), relapse during follow-up (P = 0.036), depth of invasion (P = 0.036) and the level of CA19-9 (P = 0.034). Survival analysis showed that patients negative for serum p53-Abs exhibited a prolonged disease free survival period (P log rank = 0.012). In conclusion, the secreted recombinant human P53-His produced in P. pastoris seems to be a useful antigen for detection of serum p53 Abs in patients with colorectal carcinoma.     

Culture of Staphylococcus xylosus in fish processing by‐product‐based media for lipase production

Aims: The objective of this study was to demonstrate that fish‐processing by‐products could be used as sole raw material to sustain the growth of Staphylococcus xylosus for lipase production. Methods and Results: Bacterial growth was tested on supernatants generated by boiling (100°C for 20 min) of tuna, sardine, cuttlefish and shrimp by‐products from fish processing industries. Among all samples tested, only supernatants generated from shrimp and cuttlefish by‐products sustained the growth of S. xylosus. Shrimp‐based medium gave the highest growth (A₆₀₀ = 22) after 22 h of culture and exhibited the maximum lipase activity (28 U ml^?1). This effect may be explained by better availability of nutrients, especially, in shrimp by‐products. Standard medium (SM) amendments to sardine and tuna by‐product‐based media stimulated the growth of S. xylosus and the highest A₆₀₀ values were obtained with 75% SM. Lipase activity, however, remained below 4 U ml^?1 for both sardine and tuna by‐product‐based media. Conclusions: Fish by‐products could be used for the production of highly valuable enzymes. Significance and Impact of the Study: The use of fish by‐products in producing S. xylosus‐growth media can reduce environmental problems associated with waste disposal and, simultaneously, lower the cost of biomass and enzyme production.     

HLA association with nasopharyngeal carcinoma in southern Tunisia

In order to study the association of HLA-A, -B and/or DRB1, DQB1 and the nasopharyngeal carcinoma (NPC), 141 patients affected with NPC were typed for the HLA class I by serology method of microlymphocytotoxicity. Among these patients 101 were genotyped for HLA class II system by the PCR-SSP technique. HLA typing results were compared to those of 116 controls. We found that the HLA-A31 and -A33 antigens were significantly more expressed in patients than in the controls (P = 0.016 and 0.010, respectively) and the HLA-A19 antigen, was significantly more frequent in patients when compared to the controls (P = 0.007). The HLA-DRB1*03 and DRB1*13 alleles were significantly more frequent in patients as compared to the controls. The DRB1*01 allele was expressed with a frequency of 20.69% in the controls whereas it was only detected in 3.96% of the NPC patients. Furthermore, the DQB1*05 allele was expressed at a frequency which was significantly less important in affected patient (P = 0.03), whereas, the DQB1*02 allele was more frequent in patients (P = 0.643 × 10⁻⁴). Thus our study revealed a significant increase of HLA-A31, A33, A19, B16, B53 and DRB1*03, DRB1*13 and DQB1*02 alleles in our patients. These markers could play a predisposing role in the development of NPC. In contrast, a decrease of HLA-B14, -B35 and DRB1*01 and DQB1*05 alleles was found suggesting a likely protective effect.     

Biochemical and structural comparative study between bird and mammal pancreatic colipases

Three colipases were purified from pancreas of two birds (ostrich and turkey) and one mammal (dromedary). After acidic and/or heat treatment and precipitation by sulfate ammonium and then ethanol, cofactors were purified by Sephadex G-50 gel filtration followed by ion-exchange chromatography first on Mono S and then on Mono Q. One molecular form was obtained from each species with a molecular mass of approximately 10 kDa. Cofactors were not glycosylated. The N-terminal sequences of the three purified cofactors showed high sequence homology. A 90 amino acid sequence of the ostrich cofactor was established based on peptide sequences from four different digests of the denaturated protein using trypsin, chymotrypsin, thermolysin, or staphylococcal protease. This sequence exhibited a high degree of homology with chicken and mammal cofactors. Bile salt-inhibited pancreatic lipases from five species were activated to variable extents by colipases from bird and mammal origins. The bird pancreatic lipase-colipase system appears to be functionally similar to homologous lipolytic systems from higher mammals. Our comparative study showed that mammal colipase presents a lower activation level toward bird lipases than the bird counterpart. Three-dimensional modeling of ostrich colipase suggested a structural explanation of this fact.     

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic ??,??-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI?CVII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of ??,??-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC₅₀ of 5.0 and 2.5 ??M respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 ??M.     

Prosthetic valve endocarditis: management strategies and prognosis

Background Prosthetic valve endocarditis (PVE) is a rare and serious complication after heart valve replacement; its optimal management strategy, though, still needs to be defined. Objective To study the clinical, microbiological and echocardiographic characteristics of PVE and to analyse the influence of the adopted therapeutic strategy (medical or surgical) on short- and midterm outcome in a tertiary care centre in a developing country (Tunisia). Methods All cases of PVE treated in our institution between 1997 and 2006 were retrospectively analysed according to the modified DUKE criteria. Results A total of 48 PVE episodes were diagnosed (30 men and 18 women), mean age was 37.93 years. Twenty-eight patients (58.33%) were exclusively medically treated, whereas 20 (41.66%) were treated by a combined surgical and medical strategy. Indications for surgery were haemodynamic deterioration in eight patients (40%), annular abscess in six (30%) and persisting sepsis in six (30%). In comparison with those from the medical group, operated patients had a longer delay to diagnosis (p=0.025), were more frequently in heart failure (p=0.04) and experienced more early complications (p=0.011); they also more frequently had prosthetic dehiscence (p=0.015), annular abscesses (p=0.039) and vegetations >10 mm (p=0.008). Conversely, no differences were found between the groups in terms of age, sex, or nature of involved organisms. In-hospital mortality for the medical group was 14.28% and for the surgical group 35% (p=0.09). Conclusion PVE is a very serious condition carrying high mortality rates regardless of the adopted strategy. Our study demonstrates that, in selected patients, medical treatment could be a successful and acceptable approach. (Neth Heart J 2009;17: 56-60.)     

Investigation of the steps involved in the difference of susceptibility of Ephestia kuehniella and Spodoptera littoralis to the Bacillus thuringiensis Vip3Aa16 toxin

BUPM95 is a Bacillusthuringiensis subsp. kurstaki strain producing the Vip3Aa16 toxin with an interesting insecticidal activity against the Lepidopteran larvae Ephestia kuehniella. Study of different steps in the mode of action of this Vegetative Insecticidal Protein on the Mediterranean flour moth (E. kuehniella) was carried out in the aim to investigate the origin of the higher susceptibility of this insect to Vip3Aa16 toxin compared to that of the Egyptian cotton leaf worm Spodoptera littoralis. Using E. kuehniella gut juice, protoxin proteolysis generated a major band corresponding to the active toxin and another band of about 22 kDa, whereas the activation of Vip3Aa16 by S. littoralis gut juice proteases generated less amount of the 62 kDa active form and three other proteolysis products. As demonstrated by zymogram analysis, the difference in proteolysis products was due to the variability of proteases in the two gut juices larvae. The study of the interaction of E. kuehniella BBMV with biotinylated Vip3Aa16 showed that this toxin bound to a putative receptor of 65 kDa compared to the 55 and 100 kDa receptors recognized in S. littoralis BBMV. The histopathological observations demonstrated similar damage caused by the toxin in the two larvae midguts. These results demonstrate that the step of activation, mainly, is at the origin of the difference of susceptibility of these two larvae towards B. thuringiensis Vip3Aa16 toxin.     

Finite element prediction of fatigue damage growth in cancellous bone

Cyclic stresses applied to bones generate fatigue damage that affects the bone stiffness and its elastic modulus. This paper proposes a finite element model for the prediction of fatigue damage accumulation and failure in cancellous bone at continuum scale. The model is based on continuum damage mechanics and incorporates crack closure effects in compression. The propagation of the cracks is completely simulated throughout the damaged area. In this case, the stiffness of the broken element is reduced by 98% to ensure no stress-carrying capacities of completely damaged elements. Once a crack is initiated, the propagation direction is simulated by the propagation of the broken elements of the mesh. The proposed model suggests that damage evolves over a real physical time variable (cycles). In order to reduce the computation time, the integration of the damage growth rate is based on the cycle blocks approach. In this approach, the real number of cycles is reduced (divided) into equivalent blocks of cycles. Damage accumulation is computed over the cycle blocks and then extrapolated over the corresponding real cycles. The results show a clear difference between local tensile and compressive stresses on damage accumulation. Incorporating stiffness reduction also produces a redistribution of the peak stresses in the damaged region, which results in a delay in damage fracture.