Solitary positive sentinel lymph node accompanied by negative sentinel lymph node(s) is predictive of a negative completion axillary lymph node dissection

BACKGROUND: Many patients with a positive sentinel lymph node (SLN) have a negative axillary lymph node dissection (ALND). We hypothesized that a solitary positive SLN associated with at least 1 negative SLN is predictive of a negative completion ALND. Omission of ALND may be possible in these patients. METHODS: A retrospective review of 392 consecutive patients who underwent SLNB was performed. The 78 (20%) SLN-positive patients were divided into 4 groups: group 1: solitary positive SLN associated with at least 1 negative SLN; group 2: more than 1 positive SLN with at least 1 negative SLN; group 3: solitary positive SLN with no additional SLNs; and group 4: more than 1 positive SLN and all SLNs positive. RESULTS: Excluding extracapsular extension, only 3% of group 1 patients had a positive ALND. Positive ALND was found in 15% of group 2, 29% of group 3, and 77% of group 4. CONCLUSIONS: A solitary positive SLN accompanied by additional negative SLN(s) is predictive of a negative completion ALND.     

Cancer stem cells: targets and potential biomarkers for radiotherapy

Cancer stem cells (CSC) have the unique ability to cause tumor recurrences if they survive treatment. Radiotherapy has curative potential because it has been functionally shown to sufficiently inactivate CSCs. It is well known that CSCs mediate the radiation resistance of tumors by tumor-specific factors, such as the pretreatment number of CSCs and repopulation or reoxygenation during fractionated radiotherapy. CSCs appear to have a higher intrinsic radioresistance than non-CSCs, a factor that is especially important for the development of predictive biomarkers that, if this finding holds true, can only be successfully established if they are stem-cell specific. Recent clinical data imply that stem-cell-related surface markers may be directly used as predictors for the radiocurability of tumors with comparable risk factors, such as histology and size. Future studies need to address the question of which additional markers need to be considered if more heterogeneous patient collectives are investigated. With the goal of developing a direct targeting approach, investigators are currently evaluating several drugs that are intended to target CSCs by inhibiting stem-cell-related signal transduction pathways. We need to preclinically test such drugs as combined-modality therapies in combination with radiotherapy to evaluate their curative potential, and optimize them by increasing their specificity to CSCs over normal tissue stem cells to avoid increased radiation toxicity.     

Comparison of conforming and nonconforming retrieved glenoid components

The purpose of this study was to compare differences in wear performance of conforming and nonconforming glenoid designs, using clinical, radiographic, and retrieved polyethylene glenoid component outcome Sixty-three glenoids met the study criteria, and each glenoid was assigned to the conforming group (if the radii of curvature of the humeral and glenoid components were identical) or the nonconforming group (if a mismatch existed between the radii of curvature). The mean length of implantation was 5.6 +/- 5.5 years in the conforming group and 3.1 +/- 3.1 years for the nonconforming group (P < .05). The loosening score was 3.2 +/- 2.0 in the conforming group and 2.4 +/- 1.2 in the nonconforming one (P < .05). The nonconforming group had a significantly greater burnishing score (P < .01), while the conforming group had greater abrasion and delamination scores (P < .05). Articular conformity contributes to differences observed from retrieved polyethylene glenoid components, which are consistent with differences in performance that may influence loosening.     

5,5'-Dibromo-bis(3'-indolyl)methane induces Kruppel-like factor 4 and p21 in colon cancer cells

Bis(3'-indolyl)methane (DIM) is a metabolite of the phytochemical indole-3-carbinol, and both compounds exhibit a broad spectrum of anticancer activities. We have developed a series of synthetic symmetrical ring-substituted DIM analogues, including 5,5'-dibromoDIM, which are more potent than DIM as inhibitors of cancer cell and tumor growth. In colon cancer cells, 5,5'-dibromoDIM decreased cell proliferation and inhibited G(0)-G(1)- to S-phase progression, and this was accompanied by induction of the cyclin-dependent kinase inhibitor p21 in HT-29 and RKO colon cancer cells. Mechanistic studies showed that induction of p21 in both RKO (p53 wild-type) and HT-29 (p53 mutant) cells by 5,5'-dibromoDIM was Krüppel-like factor 4 (KLF4) dependent, and induction of p53 in RKO cells was also KLF4 dependent. Analysis of the p21 promoter in p53-dependent RKO cells showed that 5,5'-dibromoDIM activated p21 gene expression through the proximal GC-rich sites 1 and 2, and chromatin immunoprecipitation assays showed that KLF4 and p53 bound to this region of the promoter, whereas in HT-29 cells unidentified upstream cis-elements were required for induction of p21. 5,5'-DibromoDIM (30 mg/kg/d) also inhibited tumor growth and induced p21 in athymic nude mice bearing RKO cells as xenografts, showing that ring-substituted DIM such as 5,5'-dibromoDIM represent a novel class of mechanism-based drugs for clinical treatment of colon cancer.     

Effect of ionic crosslinking on the drug release properties of chitosan diacetate matrices

Chitosan diacetate (CDA) was prepared by alkylating the amino moieties of chitosan with mono-iodoacetic acid. Subsequently, CDA was cross-linked with Al3+, Zn2+, and Ca2+ ions to yield three ionotropically crosslinked polymeric matrices. These composite matrices were characterized employing infrared spectroscopy (IR) and differential scanning calorimetry (DSC). Subsequently, they were loaded with caffeine, as a model drug, and were assessed as sustained release carriers by evaluating their caffeine release profiles. Interestingly, only CDA-Zn2+ complex sustained the release of caffeine effectively in a zero-order manner. The drug release and thermal behavior of the tested matrices agree with the relative strength of the ionic or coordination character of the bonds. This, in turn, depends on the position of the complexing ions on the electrophilic softness/hardness scale.     

Antimicrobial Activity of Plant Species From a Brazilian Hotspot for Conservation Priority

Serra do Cipó is part of a Brazilian bioma recently qualified as a “hotspot for conservation priority,” an area featuring exceptional concentrations of endemic species and experiencing exceptional loss of habitat. The in vitro antimicrobial activity of 20 plant species occurring in this habitat was evaluated against 4 bacteria and 2 fungal strains. About 75% of the species were active against at least one microorganism. None of the species inhibited the growing of Pseudomonas aeruginosa, Escherichia coli and Saccharomyces cerevisae. The activities of Lavoisiera cordata and Xyris pilosa extracts against Staphylococcus aureus were comparable to that of the pure antibiotic used as a positive control. The preliminary toxicity of the active extracts was evaluated by the brine shrimp lethality test and only three plants showed LD 50 values greater than 1000µg/ml, suggesting that they are relatively non-toxic. Some of the assayed plants are endangered species, presenting different degrees of extinction risk. According to our data, the plant activity against more than one microorganism seems to be advantageous to the evaluated species in protecting them against extinction.