A targetable type III immune response with increase of IL-17A expressing CD4 T cells is associated with immunotherapy-induced toxicity in melanoma.

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4 T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry.

Analysis of the PARP1, ADP-Ribosylation, and TRIP12 Triad With Markers of Patient Outcome in Human Breast Cancer.

PARP inhibitors (PARPi) are increasingly used in breast cancer therapy, including high-grade triple-negative breast cancer (TNBC) treatment. Varying treatment responses and PARPi resistance with relapse currently pose limitations to the efficacy of PARPi therapy. The pathobiological reasons why individual patients respond differently to PARPi are poorly understood.

Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma.

Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity.

Experimental Design: Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides.

Senescence Reprogramming by TIMP1 Deficiency Promotes Prostate Cancer Metastasis.

Metastases account for most cancer-related deaths, yet the mechanisms underlying metastatic spread remain poorly understood. Recent evidence demonstrates that senescent cells, while initially restricting tumorigenesis, can induce tumor progression. Here, we identify the metalloproteinase inhibitor TIMP1 as a molecular switch that determines the effects of senescence in prostate cancer.

Ultrasound Imaging of Injections in Masseter Muscle without Contrast Agent Using Strain Elastography and a Novel B-Mode Spatiotemporal Filter.

Botulinum toxin type A (BTX-A) injections in masseter muscle can alleviate muscle tightness and aching pain caused by idiopathic masticatory myalgia, a subform of the myofascial pain syndrome. Yet the injection procedure (number, amount) is currently empirical. In this ex vivo study, we determined the feasibility of using contrast-free ultrasound imaging to visualize the short-term injectate propagation.

Cancer Sample Biobanking at the Next Level: Combining Tissue With Living Cell Repositories to Promote Precision Medicine.

Biorespositories of formalin-fixed and paraffin-embedded (FFPE) or fresh frozen human tissues from malignant diseases generated as integral part of the diagnostic workup in many pathology departments have been pivotal resources for translational cancer studies. However, such tissue biobanks have traditionally contained only non-viable specimens and thus cannot enable functional assays for the discovery and validation of therapeutic targets or the assessment of drug responses and resistance to treatment. To overcome these limitations, we have developed a next-generation comprehensive biobanking platform that includes the generation of patient-derived cell models from colorectal, pancreatic and kidney cancers among others.

Perioperative considerations in Walker-Warburg syndrome.

Walker-Warburg syndrome is a rare congenital disorder. Several features, including muscular dystrophy, hydrocephalus, and oropharyngeal abnormalities, have important implications in the perioperative setting. We present a case of general anesthesia in an infant and discuss perioperative considerations to guide clinicians faced with the management of patients with this syndrome.

Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study.

Background And Objectives: The therapy and outcome of HIV infection have dramatically changed over the last 15 years, resulting in a change in renal complications. This study analyzed the characteristics of HIV-infected patients and biopsy-proven tubulointerstitial nephropathies to define disease patterns and therapeutic implications.

Design, Setting, Participants, & Measurements: A clinico-pathologic retrospective study of 59 consecutive renal biopsies showing predominant tubular and/or interstitial lesions in HIV-infected patients referred to the nephrology department between 1995 and 2011 was performed.

Whole genome and transcriptome amplification: practicable tools for sustainable tissue biobanking?

The use of whole genome amplification (WGA) and whole transcriptome amplification (WTA) techniques enables the enrichment of DNA and RNA from very small amounts of tissue. Here, we tested the suitability of WGA and WTA for tumor tissue biobanking. DNA and RNA from 13 standardized and seven non-standardized frozen and 12 formalin-fixed, paraffin-embedded (FFPE) clear cell renal cell carcinoma specimens (>9 years old) served to test the robustness of the WGA and WTA products by reidentifying von Hippel-Lindau (VHL) gene mutations known to exist in these samples.

Pathologic response to short intensified taxane-free neoadjuvant chemotherapy in patients with highly proliferative operable breast cancer.

Objectives: Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence.

Methods: Patients with early breast cancer with highly proliferative (S-phase fraction >4%) operable tumors of >3 cm received 4 cycles of intensified neoadjuvant chemotherapy with high-dose cyclophosphamide (doxorubicin 70 mg/m d1, cyclophosphamide 700 mg/m d1/d8, and 5 FU 700 mg/m d1-d5) every 3 weeks.

Unusual primary HIV infection with colonic ulcer complicated by hemorrhagic shock: a case report.

Introduction: Timely diagnosis of primary HIV infection is important to prevent further transmission of HIV. Primary HIV infection may take place without symptoms or may be associated with fever, pharyngitis or headache. Sometimes, the clinical presentation includes aseptic meningitis or cutaneous lesions.

Arginine methylation in subunits of mammalian pre-mRNA cleavage factor I.

Mammalian cleavage factor I (CF I(m)) is composed of two polypeptides of 25 kDa and either a 59 or 68 kDa subunit (CF I(m)25, CF I(m)59, CF I(m)68). It is part of the cleavage and polyadenylation complex responsible for processing the 3' ends of messenger RNA precursors. To investigate post-translational modifications in factors of the 3' processing complex, we systematically searched for enzymes that modify arginines by the addition of methyl groups.

Visceral leishmaniasis in a kidney transplant recipient: parasitic interstitial nephritis, a cause of renal dysfunction.

Visceral leishmaniasis (VL) due to Leishmania infantum is an endemic parasitic infection in the Mediterranean area. It most commonly affects immunosuppressed individuals, especially HIV patients and less frequently organ transplant recipients. Renal involvement seems to be frequent and is mostly associated with tubulointerstitial nephritis, as described in autopsy reports.

[Paraproteinemia and renal diseases].

Paraproteinaemia is frequent in the population above 50 years of age. It is commonly associated in patients with multiple myeloma with diverse renal involvements, such as cast nephropathy, light chain deposition disease, amyloidosis and Fanconi syndrome. A rapid diagnosis is necessary to implement a specific and aggressive treatment in order to prevent development of end-stage renal disease.

Papillary fibroelastoma of the left atrial wall: a case report.

Cardiac papillary fibroelastoma is a rare, benign cardiac tumor. It often arises from valvular endocardium, and non-valvular endocardial location is rare. Although transthoracic echocardiography is usually sufficient for the diagnosis of most cardiac tumors, small tumors such as papillary fibroelastoma may be missed.

[Hemolytic uremic syndrome following gemcitabine treatment].

Hemolytic uremic syndrome (HUS) in children is classically associated with diarrheas related to the production of a shiga-toxin. HUS occurs among oncologic patients, in relation with the cancer itself, or as a complication of the cytostatic treatment. The physician should be familiar with the triad of HUS (microangiopathic hemolytic anemia, thrombocytopenia and renal failure) and search actively for this pathology in oncologic patient.

A procedure for tissue freezing and processing applicable to both intra-operative frozen section diagnosis and tissue banking in surgical pathology.

Different methods for snap freezing surgical human tissue specimens exist. At pathology institutes with higher work loads, solid carbon dioxide, freezing sprays, and cryostat freezing are commonly used as coolants for diagnosing frozen tissue sections, whereas for tissue banking, liquid nitrogen or isopentane cooled with liquid nitrogen is preferred. Freezing tissues for diagnostic and research purposes are therefore often time consuming, laborious, even hazardous, and not user friendly.

[Eyelid chondroid syringoma: a case report].

Chondroid syringoma is a rare benign skin tumor of the head and neck. Only 15 cases presenting on the eyelid have been described in the literature. An 84-year-old patient presented with an 8-mm nodule on the right inferior eyelid that had grown over 5 years.

An interaction between U2AF 65 and CF I(m) links the splicing and 3' end processing machineries.

The protein factor U2 snRNP Auxiliary Factor (U2AF) 65 is an essential component required for splicing and involved in the coupling of splicing and 3' end processing of vertebrate pre-mRNAs. Here we have addressed the mechanisms by which U2AF 65 stimulates pre-mRNA 3' end processing. We identify an arginine/serine-rich region of U2AF 65 that mediates an interaction with an RS-like alternating charge domain of the 59 kDa subunit of the human cleavage factor I (CF I(m)), an essential 3' processing factor that functions at an early step in the recognition of the 3' end processing signal.

Post-conditioning by a short administration of desflurane reduced renal reperfusion injury after differing of ischaemia times in rats.

Background: 'Anaesthetic post-conditioning', that is administration of anaesthetics during early reperfusion, is known to have positive effects on several organs. For the kidney, however, the effects of post-conditioning by volatile anaesthetics are not well researched. We examined renal function and morphology after post-conditioning by desflurane.

Effect of sevoflurane preconditioning on ischaemia/reperfusion injury in the rat kidney in vivo.

Background And Objective: Whereas the protective effect of anaesthetic and ischaemic preconditioning has been described for several organs, it is uncertain whether this mechanism is also effective in the kidney. We compared the effect of preconditioning with sevoflurane and preconditioning with short episodes of ischaemia on renal ischaemia/reperfusion injury in the rat in vivo.

Methods: Fourteen days after right-sided nephrectomy, anaesthetized male Wistar rats were randomly assigned to a sham-operated group (no arterial occlusion, n = 5) or underwent 45 min of left renal artery occlusion (control group, n = 9) followed by 3 days of reperfusion.

The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo.

Volatile anesthetics induce myocardial preconditioning and can also protect the heart when given at the onset of reperfusion-a practice recently termed "postconditioning." We investigated the role of mitochondrial KATP (mKATP)-channels in sevoflurane-induced cardioprotection for both preconditioning and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion.