RNA-mediated double-strand break repair by end-joining mechanisms.

Double-strand breaks (DSBs) in DNA are challenging to repair. Cells employ at least three DSB-repair mechanisms, with a preference for non-homologous end joining (NHEJ) over homologous recombination (HR) and microhomology-mediated end joining (MMEJ). While most eukaryotic DNA is transcribed into RNA, providing complementary genetic information, much remains unknown about the direct impact of RNA on DSB-repair outcomes and its role in DSB-repair via end joining.

Optical Coherence Tomography (OCT): A Brief Look at the Uses and Technological Evolution of Ophthalmology.

Medical imaging is the mainstay of clinical diagnosis and management. Optical coherence tomography (OCT) is a non-invasive imaging technology that has revolutionized the field of ophthalmology. Since its introduction, OCT has undergone significant improvements in image quality, speed, and resolution, making it an essential diagnostic tool for various ocular pathologies.

Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome.

Abundant ribonucleoside-triphosphate (rNTP) incorporation into DNA by DNA polymerases in the form of ribonucleoside monophosphates (rNMPs) is a widespread phenomenon in nature, resulting in DNA-structural change and genome instability. The rNMP distribution, characteristics, hotspots and association with DNA metabolic processes in human mitochondrial DNA (hmtDNA) remain mostly unknown. Here, we utilize the ribose-seq technique to capture embedded rNMPs in hmtDNA of six different cell types.

Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic horizons of various cancers. However, immune-related adverse events have been reported, including interstitial lung diseases. Our aim was to describe the clinical and radiological features and survival of a multicentre cohort of patients who developed ICI-related lung toxicity.

Gene Co-Expression Analysis of Human Reveals Functional Networks Associated with DNA Replication, DNA Damage Response, and Cell Cycle Regulation.

Ribonuclease (RNase) H2 is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance, and DNA damage repair. RNase H2 is a trimer composed of three subunits, being the catalytic subunit. expression levels have been shown to be upregulated in transformed and cancer cells.

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer.

Background: Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).

Materials And Methods: Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC.

Two-point-NGS analysis of cancer genes in cell-free DNA of metastatic cancer patients.

Background: Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti-HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor.

Methods: We assessed the status of a large panel of cancer driver genes by cell-free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression.

PIK3CA-CDKN2A clonal evolution in metastatic breast cancer and multiple points cell-free DNA analysis.

Background: Daily experience tells us that breast cancer can be controlled using standard protocols up to the advent of a relapse. Now new frontiers in precision medicine like liquid biopsy of cell free DNA (cfDNA) give us the possibility to understand cancer evolution and pick up the key mutation on specific cancer driver gene. However, tight schedule of standardized protocol may impair the use of personalized experimental drugs in a timely therapeutic window.

Fatty Acids Dietary Supplements Exert Anti-Inflammatory Action and Limit Ganglion Cell Degeneration in the Retina of the EAE Mouse Model of Multiple Sclerosis.

Optic neuritis is an acute inflammatory demyelinating disorder of the optic nerve (ON) and is an initial symptom of multiple sclerosis (MS). Optic neuritis is characterized by ON degeneration and retinal ganglion cell (RGC) loss that contributes to permanent visual disability and lacks a reliable treatment. Here, we used the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, a well-established model also for optic neuritis.

Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen Activator Receptor System.

The spontaneously diabetic Torii (SDT) rat is of increasing preclinical interest because of its similarities to human type 2 diabetic retinopathy (DR). The system formed by urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is a player in blood-retinal barrier (BRB) breakdown in DR. Here, we investigated whether in SDT rats, preventive administration of UPARANT, an inhibitor of the uPAR pathway, counteracts the retinal impairment in response to chronic hyperglycemia.

The Urokinase Receptor-Derived Peptide UPARANT Recovers Dysfunctional Electroretinogram and Blood-Retinal Barrier Leakage in a Rat Model of Diabetes.

Purpose: The activation of the urokinase-type plasminogen activator and its receptor system is associated with retinal diseases. Among peptide inhibitors of this system, UPARANT acts by preventing the onset of pathologic signs of neovascular ocular diseases. We investigated whether systemic UPARANT may act in a therapeutic regimen by suppressing the retinal damage that characterizes diabetic retinopathy using a rat model of streptozotocin-induced diabetes.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting.

Late hepatic metastasis from a duodenal gastrointestinal stromal tumor (29 years after surgery): report of a case and review of the literature.

Gastrointestinal stromal tumor (GIST) metastases are found most commonly in the liver, on average 16 to 38 months after resection of the primary tumor, even if some delayed hepatic metastases from GISTs have been described. We report a case of a man with a giant liver mass at computed tomography scan. In September 1984, the patient had undergone resection of a duodenal tumor, diagnosed as schwannoma.

Exclusion of the unfolded protein response in light-induced retinal degeneration in the canine T4R RHO model of autosomal dominant retinitis pigmentosa.

Purpose: To examine the occurrence of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) following acute light damage in the naturally-occurring canine model of RHO-adRP (T4R RHO dog).

Methods: The left eyes of T4R RHO dogs were briefly light-exposed and retinas collected 3, 6 and 24 hours later. The contra-lateral eyes were shielded and used as controls.

A husband and a wife with simultaneous presentation of glioblastoma multiforme: a case report.

Glioblastoma multiforme (GBM) is the most lethal subtype of glioma, classified as a WHO grade 4 infiltrative glioma. The etiology of GBM remains unknown and risk factors can be identified only in a small minority. We report the synchronous occurrence of GBM in an otherwise unrelated married couple, i.

Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo.

Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined. Here we determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo.

Safety and potential benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal carcinomatosis from primary or recurrent ovarian cancer.

Objectives: To analyze the outcomes of cytoreductive surgery and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer.

Methods: Fifty-three patients with peritoneal carcinomatosis from primary (45 cases) and recurrent (8 cases) ovarian cancer were previously treated by systemic chemotherapy with platinum and taxanes and then submitted to surgical cytoreduction and HIPEC (cisplatin and mitomycin-C) with a closed abdomen technique. The median follow-up period was 27 months (range: 3-107).

Three-dimensional conformal radiotherapy, temozolomide chemotherapy, and high-dose fractionated stereotactic boost in a protocol-driven, postoperative treatment schedule for high-grade gliomas.

Aims And Background: No available scientific report deals with high-dose (> or = 70 Gy) radiotherapy plus temozolomide chemotherapy (TMZ CHT) in high-grade gliomas. The survival results of a protocol-driven, postoperative treatment schedule are reported here to contribute to the discussion on this issue.

Methods And Study Design: Uniform criteria were prospectively adopted for case selection during the period 1993-2006 in the management of 123 patients, and we progressively introduced three-dimensional conformal radiotherapy (3D-CRT, 60 Gy), TMZ CHT and a high-dose (70 Gy) stereotactic boost (HDSRT) in the treatment schedule.

The prognostic role of Beclin 1 protein expression in high-grade gliomas.

High-grade gliomas (HGG) have a poor outcome, however, prognostic subgroups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product.

Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the Multidisciplinary Oncology Group on Gastrointestinal Tumors.

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy.

Capecitabine as third-line treatment in patients with metastatic renal cell carcinoma after failing immunotherapy.

The aim of this study was to evaluate the activity and toxicity of capecitabine as third-line treatment in patients with advanced renal cell carcinoma for whom immunotherapy had failed. Twenty-one patients with metastatic clear renal cell carcinoma were enrolled. Capecitabine was administered orally twice daily at a dosage of 2500 mg/m(2) for 14 days, followed by 7 days of rest.

Weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer previously exposed to docetaxel.

Objective: To evaluate the activity and tolerability of weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second-line chemotherapy, but with no standard salvage therapy available we hypothesised that high-dose calcitriol might restore sensitivity to chemotherapy.

Patients And Methods: The study comprised 26 patients who had progressed after first-line treatment with docetaxel-based chemotherapy had failed. Treatment cycles consisted of calcitriol (32 microg orally as 0.

Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin.

Purpose: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy.

Methods: Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer).

FOLFOX-4 stop and go and capecitabine maintenance chemotherapy in the treatment of metastatic colorectal cancer.

Objective: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients.

Methods: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m(2) day 1, leucovorin 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) and 22 h 600 mg/m(2) days 1 and 2, every 2 weeks).

Cutaneous metastases from adenocarcinoma of the rete testis.

Adenocarcinoma of the rete testis (ACRT) is extremely rare and has only been the subject of sporadic case reports, in most of which the neoplasm manifested as a scrotal mass with diffuse enlargement of the testis. Only a few cases of scrotal infiltration by a contiguous ACRT have been described. To our knowledge, none have reported distant skin metastases.