Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Proposed national diagnostic reference levels for computed tomography examinations based on clinical indication, patient gender and size and the use of contrast in Lebanon

This study aims to propose national diagnostic reference levels (DRLs) for computed tomography (CT) scans performed on adult patients based on clinical indication (CI), patient gender and size and the use of contrast in Lebanon. The volume CT dose index (CTDIvol), size-specific dose estimate (SSDE) and dose length product (DLP) were collected between July 2017 and May 2022 from 14 Lebanese hospitals. The data were collected from at least 20 patients for 15 common group of CIs (GCIs) in the head, thorax, abdomen (AB), abdomen-pelvis (ABP) and thorax-abdomen-pelvis (TABP) regions. National DRLs were calculated for each GCIs, patient gender and size and depending on the use of contrast as the third quartile of the CT units’ median values of CTDIvol, SSDE and DLP. The proposed national DRLs in term of CTDIvol (DLP) were 65, 15, 9, 9 and 13 mGy (1104, 483, 520, 442 and 611 mGy.cm), respectively, for Head/Hemorrhage, ABP/Appendicitis, AB/Abdominal pain, Thorax/Covid-19 and TABP/Trauma. The proposed national DRLs were higher than those from the literature pointing up the need for a dose optimization strategy to protect the patient from the harmful effects of radiation

Effect of orientation and crystallization on dielectric and mechanical relaxations in uniaxially stretched poly(ethylene naphthalene 2,6 dicarboxylate)(PEN) films

International audienc

Uniaxially stretched poly(ethylene naphthalene 2,6-dicarboxylate) films studied by broadband dielectric spectroscopy

International audienc