Validation of a SPE HPLC-UV method for the quantification of a new ER-specific photosensitizer OR-141 in blood serum using total error concept.

The aim of this work is to develop the first validated HPLC-UV method quantification in blood serum for a new endoplasmic reticulum (ER)-specific benzophenazine photosensitizer (OR-141). A fast solid phase extraction (SPE) cleaning sample procedure was achieved on C18 encapped (ec) SPE cartridges and the separation was performed on a RP-18e column (5μM) using an isocratic elution with methanol. The method has been fully validated according to accuracy profiles based on total error and tolerance intervals.

A new ER-specific photosensitizer unravels (1)O2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT.

Photosensitizers (PS) are ideally devoid of any activity in the absence of photoactivation, and rely on molecular oxygen for the formation of singlet oxygen ((1)O2) to produce cellular damage. Off-targets and tumor hypoxia therefore represent obstacles for the use of PS for cancer photodynamic therapy. Herein, we describe the characterization of OR141, a benzophenazine compound identified through a phenotypic screening for its capacity to be strictly activated by light and to kill a large variety of tumor cells under both normoxia and hypoxia.

Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

Unlabelled: Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases.

Structural determinants of specificity and catalytic mechanism in mammalian 25-kDa thiamine triphosphatase.

Background: Thiamine triphosphate (ThTP) is present in most organisms and might be involved in intracellular signaling. In mammalian cells, the cytosolic ThTP level is controlled by a specific thiamine triphosphatase (ThTPase), belonging to the CYTH superfamily of proteins. CYTH proteins are present in all superkingdoms of life and act on various triphosphorylated substrates.

High inorganic triphosphatase activities in bacteria and mammalian cells: identification of the enzymes involved.

Background: We recently characterized a specific inorganic triphosphatase (PPPase) from Nitrosomonas europaea. This enzyme belongs to the CYTH superfamily of proteins. Many bacterial members of this family are annotated as predicted adenylate cyclases, because one of the founding members is CyaB adenylate cyclase from A.

A specific inorganic triphosphatase from Nitrosomonas europaea: structure and catalytic mechanism.

The CYTH superfamily of proteins is named after its two founding members, the CyaB adenylyl cyclase from Aeromonas hydrophila and the human 25-kDa thiamine triphosphatase. Because these proteins often form a closed β-barrel, they are also referred to as triphosphate tunnel metalloenzymes (TTM). Functionally, they are characterized by their ability to bind triphosphorylated substrates and divalent metal ions.

Thiaminylated adenine nucleotides. Chemical synthesis, structural characterization and natural occurrence.

Thiamine and its three phosphorylated derivatives (mono-, di- and triphosphate) occur naturally in most cells. Recently, we reported the presence of a fourth thiamine derivative, adenosine thiamine triphosphate, produced in Escherichia coli in response to carbon starvation. Here, we show that the chemical synthesis of adenosine thiamine triphosphate leads to another new compound, adenosine thiamine diphosphate, as a side product.

Strain accommodation by slow slip and dyking in a youthful continental rift, East Africa.

Continental rifts begin and develop through repeated episodes of faulting and magmatism, but strain partitioning between faulting and magmatism during discrete rifting episodes remains poorly documented. In highly evolved rifts, tensile stresses from far-field plate motions accumulate over decades before being released during relatively short time intervals by faulting and magmatic intrusions. These rifting crises are rarely observed in thick lithosphere during the initial stages of rifting.

Menstrual activity of matrix metalloproteinases is decreased in endometrium regenerating after thermal ablation.

Background: Menstruation is associated with a striking increase in matrix metalloproteinase (MMP) activity. However, it is still unknown whether the level of MMP activity correlates with the amount of menstrual bleeding.

Methods: We used histochemistry to investigate the degradation of the extracellular matrix (ECM), and immunohistochemical labelling and zymographic analysis to determine the level of expression and activity of MMP-2 and -9, and of their tissue inhibitors (TIMPs) -1, -2 and -3, in endometria sampled during menstruation in 14 women experiencing excessive menstrual bleeding and in 10 women successfully treated for menorrhagia by thermal ablation of the endometrium.

Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

Context: Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown.

Opposite regulation of transforming growth factors-beta2 and -beta3 expression in the human endometrium.

TGF-betas have been reported to mediate the repression by progesterone of several matrix metalloproteinases in the human endometrium, thereby preventing menstrual breakdown. Because of conflicting reports on the expression profiles, source, and regulation of the TGF-beta system in this tissue, we investigated by real-time RT-PCR and ELISA the expression of the three TGF-betas (total and mature forms) and their two receptors throughout the menstrual cycle, and their regulation by ovarian steroids in cultured explants including their microdissected epithelial and stromal compartments. Regulation by cAMP and MAPK was further investigated.

Response of matrix metalloproteinases and tissue inhibitors of metalloproteinases messenger ribonucleic acids to ovarian steroids in human endometrial explants mimics their gene- and phase-specific differential control in vivo.

Context: Cyclic remodeling and breakdown of the extracellular matrix, a unique feature of the human endometrium, depends on matrix metalloproteinases (MMPs). These enzymes are globally controlled by estradiol and progesterone or their withdrawal, but various MMPs and their tissue inhibitors (TIMPs) show distinct responses.

Objective And Design: To clarify the role of ovarian steroids in the differential regulation of MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, TIMP-1, TIMP-2, and TIMP-3 mRNAs, we compared their variations in the cycling endometrium in vivo with their response to hormone addition or withdrawal in corresponding explants.

[Bone metastasis of a prostate tumor and osteosynthesis material. A case report].

The detection of metastatic deposits at the site of previous osteosynthesis is difficult. Bone imaging and scanning with technectium 99m are unhelpful in differentiating between osteomyelitis, Paget's disease and a bone metastasis. The authors present details of a patient who had undergone osteosynthesis for a fracture of the left tibia in 1983.

The operative treatment of intraarticular calcaneal fractures. Indications, technique, and results in 257 cases.

Since 1972, 257 intraarticular fractures of the calcaneus have been treated with operative intervention. A lateral incision and a third tubular plate were used in all cases. The functional results were considered excellent or good in 85%, and there was an infection rate of 2.

Triflusal versus acetylsalicylic acid: a double-blind study for the prophylaxis of deep vein thrombosis after hip surgery.

The authors report the results of a randomised double-blind study comparing the antithrombotic activity of a new anti-platelet drug (Triflusal) with that of acetylsalicylic acid (ASA). 99 patients who underwent hip surgery were included in the study (total hip replacement, osteosynthesis of a pertrochanter fracture or Moore's prosthesis for intracapsular fracture of the femoral neck). Of the 48 patients having received Triflusal, 7 (14.

[Osteosynthesis of lesions of the proximal femur using dynamic screw plates. Multicenter study: 1871 cases].

A series of 1871 lesions of the upper end of the femur were treated in 32 hospitals in Belgium using a dynamic hip screw. Unstable pertrochanteric fractures were present in 34.4%.