Breast metastasis from squamous cell carcinoma of the oropharynx: a case report

Background

Breast metastases from extramammary tumors are extremely rare, the most common primary tumors being contralateral breast carcinoma, followed by lung, gynecological, gastrointestinal, melanoma, and hematological cancers. Only a few cases deriving from head and neck squamous cell carcinoma have been reported in the literature to date.

Case presentation

We report a case of a 47-year-old Caucasian woman who presented to our hospital with a solitary breast lesion in the right upper external quadrant associated with multiple bone and visceral metastases. Two years before, she had undergone radical resection of a squamous cell carcinoma of the oropharynx (stage pT2, pN1), which was followed by adjuvant radiotherapy. Breast ultrasound showed a hypoechogenic tumor lesion of 4 cm in the right upper external quadrant that was associated with multiple axillary and infra-/supraclavicular adenopathies. A positron emission tomographic scan documented multiple visceral and bone metastases with a single hypermetabolic lesion of the right breast. The results of histology and immunohistochemistry were consistent with a metastasis from a squamous cell carcinoma. The patient died of acute respiratory insufficiency 1 month after her breast metastasis diagnosis and before starting any systemic antitumoral treatment.

Conclusions

Although breast metastases are extremely rare, they should be considered in any patient with a history of cancer and confirmed by histology and immunohistochemistry because they are very difficult to distinguish from other primary breast tumors based only on clinical and radiological features. There are no standardized treatment guidelines for breast metastasis management. Surgery and radiotherapy can play a role in symptom palliation, but they do not have any relevant impact on survival, the prognosis being poor, with an estimated overall survival less than 1 year from diagnosis.

     

Decomposition dynamics of Phragmites australis litter in Lake Burullus,Egypt

This study estimated the decomposition rate and nutrient dynamics of Phragmites australis litter in Lake Burullus (Egypt) and investigated the amount of nutrients released back into the water after the decomposition of the dead tissues. Phragmites australis detritus decomposition was studied from April to September 2003 utilizing the leaf, stem, and rhizome litterbags technique with coarse mesh (5 mm) bags on five sampling dates and with nine replicate packs per sample. All samples were dried, weighed and analyzed for N, P, Ca, Mg, Na, and K concentrations. The exponential breakdown rate of leaves (?0.0117/day) was significantly higher than that of rhizomes (?0.0040/day) and stems (?0.0036/day). N, Na and K mineralization were the highest from leaf litter, followed by rhizomes and stems, while P, Ca and Mg mineralization were the highest from rhizomes, followed by leaves and stems. The dead shoot biomass at the end of 2003 amounted to 4550 g DM/m² which enters the decomposition process. By using the decay rate of 0.0117 and 0.0036/day for the leaves and stems, 3487 g DM/m² is decomposed in a year, leaving only 1063 g DM/m² after 1 year. This is mainly equivalent to releasing the following nutrients into surrounding water (in g/m²): 24.4 N, 1.1 P, 15.5 Ca, 3.5 Mg, 11.3 Na and 16.7 K. In conclusion, the present study indicates a significant difference in relation to the type of litter; these breakdown rates were generally greater than most rates reported in previous studies that used the same technique and mesh size.     

Bioaccumulation and rhizofiltration potential of Pistia stratiotes L. for mitigating water pollution in the Egyptian wetlands

The bioaccumulation and rhizofiltration potential of P. stratiotes for heavy metals were investigated to mitigate water pollution in the Egyptian wetlands. Plant and water samples were collected monthly through nine quadrats equally distributed along three sites at Al-Sero drain in Giza Province. The annual mean of the shoot biomass was 10 times that of the root. The concentrations of shoot heavy metals fell in the order: Fe < Mn < Cr < Pb < Cu < Zn < Ni < Co < Cd, while that of the roots were: Fe < Mn < Cr < Pb < Zn < Ni < Co < Cu < Cd. The bio-concentration factor (BCF) of most investigated heavy metals, except Cr and Pb, was greater than 1000, while the translocation factor (TF) of most investigated metals, except Pb and Cu, did not exceed one. The rhizofiltration potential (RP) of heavy metals was higher than 1000 for Fe, and 100 for Cr, Pb and Cu. Significant positive correlations between Fe and Cu in water with those in plant roots and leaves, respectively were recorded, which, in addition to the high BCF and RP, indicate the potential use of P. stratiotes in mitigating these toxic metals.     

The relationship between preimplantation morphokinetics of human embryos and sex chromosome pattern

The aim of this study was to determine the relationship between the gender of human embryos and chronological changes during the two pronuclear (2PN) embryonic stage and blastocyst formation on day five after injection using time-lapse imaging and preimplantation genetic testing. A total of 120 couples who underwent intracytoplasmic sperm injection with preimplantation genetic testing were included in the study. Only normal embryos (n?=?416) were enrolled in this study. Time-lapse imaging data of male (n?=?227) and female (n?=?189) embryo progression was carried out to estimate the times of initial appearance of the 2PN stage, fading times and day five blastulation rates. The results revealed that the 2PN stage (fertilisation) was reached significantly earlier in female embryos (9.09?±?1.31?h) than in male embryos (9.52?±?1.48?h, p-value?=?0.0044). Conversely, the fading time of 2PN was significantly faster in male embryos (22.13?±?2.02) than in female embryos (24.16?±?2.61, p-value < 0.001). The blastulation rate was significantly higher in female than male embryos (68.25% vs. 57.71%; p-value?=?0.025).     

Disruption in the autophagic process underlies the sensory neuropathy in dystonia musculorum mice

A homozygous mutation in the DST (dystonin) gene causes a newly identified lethal form of hereditary sensory and autonomic neuropathy in humans (HSAN-VI). DST loss of function similarly leads to sensory neuron degeneration and severe ataxia in dystonia musculorum (Dst^dt) mice. DST is involved in maintaining cytoskeletal integrity and intracellular transport. As autophagy is highly reliant upon stable microtubules and motor proteins, we assessed the influence of DST loss of function on autophagy using the Dst^dt-Tg4 mouse model. Electron microscopy (EM) revealed an accumulation of autophagosomes in sensory neurons from these mice. Furthermore, we demonstrated that the autophagic flux was impaired. Levels of LC3-II, a marker of autophagosomes, were elevated. Consequently, Dst^dt-Tg4 sensory neurons displayed impaired protein turnover of autophagosome substrate SQTSM1/p62 and of polyubiquitinated proteins. Interestingly, in a previously described Dst^dt-Tg4 mouse model that is partially rescued by neuronal specific expression of the DST-A2 isoform, autophagosomes, autolysosomes, and damaged organelles were reduced when compared to Dst^dt-Tg4 mutant mice. LC3-II, SQTSM1, polyubiquitinated proteins and autophagic flux were also restored to wild-type levels in the rescued mice. Finally, a significant decrease in DNAIC1 (dynein, axonemal, intermediate chain 1; the mouse ortholog of human DNAI1), a member of the DMC (dynein/dynactin motor complex), was noted in Dst^dt-Tg4 dorsal root ganglia and sensory neurons. Thus, DST-A2 loss of function perturbs late stages of autophagy, and dysfunctional autophagy at least partially underlies Dst^dt pathogenesis. We therefore conclude that the DST-A2 isoform normally facilitates autophagy within sensory neurons to maintain cellular homeostasis.     

Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.     

Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

Background

Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population.

Design

MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study.     

Targeting MAPKs,NF-κB,and PI3K/AKT pathways by methyl palmitate ameliorates ethanol-induced gastric mucosal injury in rats

Excessive drinking of alcohol has been frequently associated with gastric injury; however, its underlying molecular mechanisms have been inadequately investigated. Methyl palmitate (MP) has demonstrated marked hepato-, cardio- and pulmonary protective features; however, its effects on ethanol-induced gastric injury have not been studied. The aim of the present study was to evaluate the potential gastroprotective activity of MP against ethanol-evoked gastric mucosal damage in rats and associated molecular mechanisms, for example, mitogen-activated protein kinases (MAPKs), nuclear factor κB (NF-κB), and phosphoinositide 3 kinase/protein kinase B (PI3K/AKT) pathways. The rat stomachs were examined in terms of the inflammatory, oxidative, and apoptotic perturbations. Current data demonstrated that pretreatment with MP attenuated the gross gastric damage, scores of ulcer index, area of mucosal lesions and histopathology outcomes; actions which were similar to the reference antiulcer omeprazole. MP inhibited NF-κB expression, its nuclear translocation, and the expression of its downstream signals, for example, tumor necrosis factor-α and myeloperoxidase besides restoration of interleukin-10 levels. Western blot analysis revealed that MP counteracted the disruption of MAPKs signaling via lowering p-c-Jun N-terminal kinase 1/2 (p-JNK1/2) expression and restoring the phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) levels without affecting p-p38MAPK levels. Additionally, MP improved the antioxidant milieu via diminishing lipid peroxides and enhancing glutathione, glutathione peroxidase, total antioxidant capacity and mucosal nitric oxide. In the context of apoptosis, MP inhibited the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP) and Bax protein expression with upregulating B cell lymphoma-2 expression (Bcl-2), thus, promoting gastric cellular survival. This was confirmed by MP activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K p110α and p-AKT. Together, the present findings report the gastroprotective actions of MP mediated via its anti-inflammatory, antioxidant, and antiapoptotic actions. The underlying molecular mechanisms involve, at least partly, the modulation of MAPKs, NF-κB and PI3K/AKT transduction.     

Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity

A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay.