Role of the cellular factor CTCF in the regulation of bovine leukemia virus latency and three-dimensional chromatin organization.

Bovine leukemia virus (BLV)-induced tumoral development is a multifactorial phenomenon that remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the provirus.

Jurkat-Derived (J-Lat, J1.1, and Jurkat E4) and CEM-Derived T Cell Lines (8E5 and ACH-2) as Models of Reversible Proviral Latency.

The introduction of combination antiretroviral therapy (cART) has switched HIV-1 infection from a lethal disease to a chronic one. Indeed, cART is a lifelong treatment since its interruption is always followed by a rapid rebound of viremia from both cellular and anatomical viral reservoirs where the integrated HIV-1 provirus remains transcriptionally silent or maintains low-levels of viral replication, thereby preventing HIV-1 eradication. As therapeutic approach, the "shock and kill" strategy has emerged with the main objective to reactivate HIV-1 transcription from latency by using latency reversing agents (LRAs) prior to kill the reactivated infected cells by improving host immune responses.

The Current Status of Latency Reversing Agents for HIV-1 Remission.

Combinatory antiretroviral therapy (cART) reduces human immunodeficiency virus type 1 (HIV-1) replication but is not curative because cART interruption almost invariably leads to a rapid rebound of viremia due to the persistence of stable HIV-1-infected cellular reservoirs. These reservoirs are mainly composed of CD4 T cells harboring replication-competent latent proviruses. A broadly explored approach to reduce the HIV-1 reservoir size, the shock and kill strategy, consists of reactivating HIV-1 gene expression from the latently infected cellular reservoirs (the shock), followed by killing of the virus-producing infected cells (the kill).

Shocking HIV-1 with immunomodulatory latency reversing agents.

The "shock-and-kill" strategy is one of the most explored HIV-1 cure approaches to eliminate latent virus. This strategy is based on HIV-1 reactivation using latency reversing agents (LRAs) to reactivate latent proviruses (the "shock" phase) and to induce subsequent elimination of the reactivated cells by immune responses or virus-induced cytopathic effects (the "kill" phase). Studies using immunomodulatory LRAs such as blockers of immune checkpoint molecules, toll-like receptor agonists, cytokines and CD8 T cell depleting antibodies showed promising potential as LRAs inducing directly or indirectly cellular pathways known to control HIV transcription.

[Predictive scores used during the anesthetic preoperative visit. Part 2. Assessment of perioperative risk].

Anesthesia remains a high-risk specialty, even though the discipline has evolved considerably over the last few decades. Independently of postoperative complications, some risks are inherent to the perioperative period itself. In this narrative review of the literature, we describe these risks and the predictive scores, allowing an assessment of these complications.

[Predictive scores used during the anesthetic preoperative visit. Part 1. Assessment of postoperative complications].

Anesthesia is changing, moving from an intraoperative medicine to a transversal perioperative medicine. The evolution of the preoperative anesthetic consultation is part of this evolution. Recently, anesthesiologists attempt to categorize their patients to detect as early as possible those at risk of short, medium, and long-term complications.

Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage.

HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription.

Depicting HIV-1 Transcriptional Mechanisms: A Summary of What We Know.

Despite the introduction of combinatory antiretroviral therapy (cART), HIV-1 infection cannot be cured and is still one of the major health issues worldwide. Indeed, as soon as cART is interrupted, a rapid rebound of viremia is observed. The establishment of viral latency and the persistence of the virus in cellular reservoirs constitute the main barrier to HIV eradication.

Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites.

Human T-lymphotropic Virus type 1 (HTLV-1) infection is characterized by viral latency in the majority of infected cells and by the absence of viremia. These features are thought to be due to the repression of viral sense transcription in vivo. Here, our in silico analysis of the HTLV-1 Long Terminal Repeat (LTR) promoter nucleotide sequence revealed, in addition to the four Sp1 binding sites previously identified, the presence of two additional potential Sp1 sites within the R region.

Characterization of new RNA polymerase III and RNA polymerase II transcriptional promoters in the Bovine Leukemia Virus genome.

Bovine leukemia virus latency is a viral strategy used to escape from the host immune system and contribute to tumor development. However, a highly expressed BLV micro-RNA cluster has been reported, suggesting that the BLV silencing is not complete. Here, we demonstrate the in vivo recruitment of RNA polymerase III to the BLV miRNA cluster both in BLV-latently infected cell lines and in ovine BLV-infected primary cells, through a canonical type 2 RNAPIII promoter.

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus.

V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus.

[Usefulness of gallium 67 in research into the need for radical cervical lymph node dissection in patients with head and neck carcinomas].

Fifty-nine patients with head and neck carcinoma were examined with 67Ga scintigraphy. All patients had undergone lymph node dissection of the neck. They were followed for a minimum of 2 years after the examination.

Lack of efficacy of lymphoscintigraphy in detecting axillary lymph node metastases from breast cancer.

Preoperative detection of metastases in regional lymph nodes should constitute a fundamental step towards a better management of breast cancer. The National Cancer Institute of Milan has traditionally been engaged in this particular problem, that is, the search for a new imaging technique for detecting lymph nodal metastases from breast cancer. In 1984 axillary lymphoscintigraphy was performed on 26 patients with operable breast cancer by periareolar injection of 100 mu Ci of 99mTc sulphur microcolloid.

Transient left homonymous hemianopsia during treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin.

This is the third case, reported in the literature, of transient cortical blindness that occurred during treatment of testicular carcinoma with cisplatinum, vinblastine and bleomycin. The presence of transiently pathological computerized tomography and brain scan suggests that this alarming event may not only be a toxic side effect of chemotherapy, but also a symptom related to eradicable subclinical metastases.

[Radiographic semeiotics of bone metastasis in thyroid carcinoma].

It's well-known that thyroid malignant cancer often metastatizes to skeletal structures. Analysing a wide casuistry of the National Cancer Institute of Milan, we thought right not only consider most common iconographic findings of these bone metastases, but rarest too. Therefore, we studied many radiological symptoms: osteolysis and its shape; extension in the next soft tissues; absence of the periosteal reaction; some resemblances with other primitive cancer or secondary too and dysplasic focus; the changes after therapy usually give a not univocal interpretation of the pictures regarding these peculiar alterations.

Laser oncology in Italy: experimental research and clinical applications at the National Cancer Institute, Milan.

CO2, Nd:YAG, and argon lasers have been used for 5 years for experimental and clinical procedures at the National Cancer Institute of Milan under the auspices of the National Research Council. Experimental data regarding tumor cell spread through lymphatic and hematic channels and cell viability in the fumes after CO2 laser irradiation are reported. New advantages in the combined treatment modalities have been demonstrated, since the synergism between the low power argon laser beam and chemotherapeutic agents (anthracyclines) was assessed on cell cultures and the least toxic and the most effective doses of the drugs were identified.

Association of CEA test and liver scan in detection of hepatic metastases of gastrointestinal carcinoma.

The authors evaluate the combined use of liver scan and the CEA test in the diagnosis of hepatic metastases of carcinoma of the gastrointestinal tract. Association of the two tests is justified by the fact that the liver scan is very specific but not very sensitive, whereas the CEA test is more sensitive and not very specific. The sensitivity of the CEA test, on the other hand, can be increased by increasing the threshold of normality.

Microsphere angiography in hepatic artery infusion for cancer.

99mTc-human albumin microspheres were injected at a slow rate into the hepatic arteries of 24 patients before starting intraarterial chemotherapy for liver cancer. The distribution patterns of radiolabeled microspheres were significantly different from those obtained in contrast angiography in 13 of 22 patients. Liver uptake of slowly injected microspheres was greater than 75% in 16 of 24 patients and less than 25% in 4 of 24 patients.

[Clinical examination and 131 Cs scanning in the diagnosis of cold nodules of the thyroid (author's transl)].

The usefulness of 131Cs scanning in preoperative diagnosis of 131I cold nodules of the thyroid that present no clear clinical sign of malignancy is discussed. The results of clinical examination of 283 thyroid nodules, associated in 139 cases with 131Cs scanning, are correlated with the histologic nature. In nodules that were classifided as cold, warm or hot in the 131Cs scan, the incidence of malignancy was 2.