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Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days–19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.

Background In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether a liquid biopsy that analyses blood derived exosomal hTERT transcript (e‐hTERT‐trans) may serve as such a biomarker in gliomas and meningiomas when compared to healthy controls. Methods Exosomes were isolated from the pre‐operative sera of patients' samples stored in the biobank of both Rabin and Sheba Medical Centers. The levels of e‐hTERT‐trans were measured in 81 healthy controls, 117 meningiomas, 17 low‐grade gliomas, and 61 glioblastomas. Clinical parameters of the patients were collected retrospectively and compared to the levels of the e‐hTERT‐trans. Results The upper normal limit of controls e‐hTERT‐trans was 1.85 relative quantitation (RQ). The rate of detection increased with rising tumor grade and correlated with tumor recurrence in meningiomas: mean RQ without recurrence (2.17 ± 11.7) versus with recurrence (3.59 ± 4.42; p = 0.002). In glioblastomas, preoperative measurements correlated with tumor volume and with the disease course on serial sampling. Conclusions We demonstrated for the first time that the expression of e‐hTERT‐trans transcript can be measured in the serum of primary brain tumors. This exosomal marker carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters. Future studies are required to investigate whether the sensitivity could be augmented and whether it can be implemented into routine patients care. Our study demonstrates for the first time that the expression of hTERT mRNA transcript can be measured in the serum of both meningioma and glioma patients. As it correlated with tumor recurrence in meningiomas and with tumor volume and the disease course in glioblastomas it carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters.

Background Numerous case studies have reported spontaneous regression of recognized metastases following primary tumor excision, but underlying mechanisms are elusive. Here, we present a model of regression and latency of metastases following primary tumor excision and identify potential underlying mechanisms. Results Using MDA-MB-231 HM human breast cancer cells that express highly sensitive luciferase, we monitored early development stages of spontaneous metastases in BALB/c nu/nu mice. Removal of the primary tumor caused marked regression of micro-metastases, but not of larger metastases, and in vivo supplementation of tumor secretome diminished this regression, suggesting that primary tumor-secreted factors promote early metastatic growth. Correspondingly, MDA-MB-231 HM -conditioned medium increased in vitro tumor proliferation and adhesion and reduced apoptosis . To identify specific mediating factors, cytokine array and proteomic analysis of MDA-MB-231 HM secretome were conducted. The results identified significant enrichment of angiogenesis, growth factor binding and activity, focal adhesion, and metalloprotease and apoptosis regulation processes. Neutralization of MDA-MB-231 HM -secreted key mediators of these processes, IL-8, PDGF-AA, Serpin E1 (PAI-1), and MIF, each antagonized secretome-induced proliferation. Moreover, their in vivo simultaneous blockade in the presence of the primary tumor arrested the development of micro-metastases. Interestingly, in the METABRIC cohort of breast cancer patients, elevated expression of Serpin E1, IL-8, or the four factors combined predicted poor survival. Conclusions These results demonstrate regression and latency of micro-metastases following primary tumor excision and a crucial role for primary tumor secretome in promoting early metastatic growth in MDA-MB-231 HM xenografts. If generalized, such findings can suggest novel approaches to control micro-metastases and minimal residual disease.

Histiocytic sarcoma is a rare, lymphohematopoietic malignant neoplasm composed of tumor cells showing morphologic and immunophenotypic features of mature tissue histiocytes. Involvement of the central nervous system (CNS) as either a part of a systemic disease or as a primary lesion has rarely been described so far. We present a case of primary CNS histiocytic sarcoma in an adult patient and review the literature on this rare entity.

Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. BMC Biol 18, 198 (2020). https://doi.org/10.1186/s12915-020-00932-y Download citation * Published: 16 December 2020 * DOI: https://doi.org/10.1186/s12915-020-00932-y [RAW_REF_TEXT] Publisher Correction [/RAW_REF_TEXT] [RAW_REF_TEXT] Open Access [/RAW_REF_TEXT] [RAW_REF_TEXT] Published:16 December 2020 [/RAW_REF_TEXT] Publisher Correction: Spontaneous regression of micro-metastases following primary tumor excision: a critical role for primary tumor secretome [RAW_REF_TEXT] Lee Shaashua1 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Anabel Eckerling1 na1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Boaz Israeli1 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Gali Yanovich2 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Ella Rosenne1 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Suzana Fichman-Horn3 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Ido Ben Zvi4 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Liat Sorski1 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Rita Haldar1 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Ronit Satchi-Fainaro5 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Tamar Geiger2 , [/RAW_REF_TEXT] [RAW_REF_TEXT] Erica K. Sloan6 & [/RAW_REF_TEXT] [RAW_REF_TEXT] Shamgar Ben-Eliyahu 1 [/RAW_REF_TEXT] BMC Biology volume 18, Article number: 198 (2020) Cite this article [RAW_REF_TEXT] 8 Accesses [/RAW_REF_TEXT] [RAW_REF_TEXT] Metrics details [/RAW_REF_TEXT] [RAW_REF_TEXT] The original article was published in BMC Biology 2020 18:163 [/RAW_REF_TEXT] Correction to: BMC Biol 18, 163 (2020) https://doi.org/10.1186/s12915-020-00893-2 The original publication of this article [1] contained an incorrect version of figure 4, and an incorrect version of figure S4 in Additional file 1. Protein levels were classified as higher or lower than the median, and the association to 10-year survival was assessed by the Kaplan-Meier analysis (n = 952 per group). p value was calculated using two-sided log rank test Full size image Publisher Correction Open Access Published:16 December 2020 [/RAW_REF_TEXT] Publisher Correction: Spontaneous regression of micro-metastases following primary tumor excision: a critical role for primary tumor secretome [RAW_REF_TEXT] Lee Shaashua1 na1, Anabel Eckerling1 na1, Boaz Israeli1 , Gali Yanovich2 , Ella Rosenne1 , Suzana Fichman-Horn3 , Ido Ben Zvi4 , Liat Sorski1 , Rita Haldar1 , Ronit Satchi-Fainaro5 , Tamar Geiger2 , Erica K. Sloan6 & Shamgar Ben-Eliyahu 1 [/RAW_REF_TEXT] BMC Biology volume 18, Article number: 198 (2020) Cite this article [RAW_REF_TEXT] 8 Accesses Metrics details The original article was published in BMC Biology 2020 18:163

•A population-based study describing sarcoma incidence in Israel.•Concordance of 90 % between pathology coding and registry in the national database.•Sarcoma incidence is 8/100 K persons, and has a downward trend in the past 2 decades.•Kaposi sarcoma has the highest incidence – 1.6/100 K persons. This report aimed to describe sarcoma incidence and subtype distribution in Israel, as well as evaluate accuracy of registration for sarcoma cases diagnosed at a single institution. Incidence reports were issued for all sarcomas diagnosed between 1996–2017. Concordance between the WHO classification used in pathology reports and the diagnoses in the national registry were evaluated. Sarcoma subtype distribution was analysed. Between 1996–2017 sarcomas had an annual percent change of −2.1 in men and −1.5 in women. Concordance between the pathology report coding and registry in the INCR were 90 %. The most common subtypes were Kaposi sarcoma (KS), liposarcoma and leiomyosarcoma accounting for 21 %, 14.4 % and 10.8 % of all sarcomas, respectively. KS had the highest incidence with 1.6/100,000 persons. This is the first description of sarcoma incidence and subtype distribution in Israel. Sarcoma incidence in Israel has declined in the past two decades.

Background Aiming to clarify the mechanism of weight loss after the restrictive bariatric procedure of sleeve gastrectomy (LSG), the volumes and pressures of the stomach, of the removed part, and of the remaining sleeve were measured in 20 morbidly obese patients. Methods The technique used consisted of occlusion of the pylorus with a laparoscopic clamp and of the gastroesophageal junction with a special orogastric tube connected to a manometer. Instillation of methylene-blue-colored saline via the tube was continued until the intraluminal pressure increased sharply, or the inflated stomach reached 2,000 cc. After recording of measurements, LSG was performed. Results Mean volume of the entire stomach was 1,553 cc (600–2,000 cc) and that of the sleeve 129 cc (90–220 cc), i.e., 10% (4–17%) and that of the removed stomach was 795 cc (400–1,500 cc). The mean basal intragastric pressure of the whole stomach after insufflations of the abdominal cavity with CO 2 to 15 mmHg was 19 mmHg (11–26 mmHg); after occlusion and filling with saline it was 34 mmHg (21–45 mmHg). In the sleeved stomach, mean basal pressure was similar 18 mmHg (6–28 mmHg); when filled with saline, pressure rose to 43 mmHg (32–58 mmHg). The removed stomach had a mean pressure of 26 mmHg (12–47 mmHg). There were no postoperative complications and no mortality. Conclusions The notably higher pressure in the sleeve, reflecting its markedly lesser distensibility compared to that of the whole stomach and of the removed fundus, indicates that this may be an important element in the mechanism of weight loss.

Background In recent years, laparoscopic sleeve gastrectomy (LSG) as a single-stage procedure for the treatment of morbid obesity is becoming increasingly popular. Of continuing concern are the rate of postoperative complications and the lack of consensus as to surgical technique. Methods A prospective study assessment was made of 120 consecutive morbidly obese patients with body mass index (BMI) of 43 ± 5 (30 to 63), who underwent LSG using the following technique: (1) division of the vascular supply of the greater gastric curvature and application of the linear stapler-cutter device beginning at 6–7 cm from the pylorus so that part of the antrum remains; (2) inversion of the staple line by placement of a seroserosal continuous suture close to the staple line; (3) use of a 48 Fr bougie so as to avoid possible stricture; (4) firing of the stapler parallel to the bougie to make the sleeve as narrow as possible and prevent segmental dilatation. Results Intraoperative difficulties were encountered in four patients. There were no postoperative complications—no hemorrhage from the staple line, no anastomotic leakage or stricture, and no mortality. In 20 patients prior to the sleeve procedure, a gastric band was removed. During a median follow-up of 11.7 months (range 2–31 months), percent of excess BMI lost reached 53 ± 24% and the BMI decreased from 43 ± 5 to 34 ± 5 kg/m 2 . Patient satisfaction scoring (1–4) at least 1 year after surgery was 3.6 ± 0.8. Conclusions The good early results obtained with the above-outlined surgical technique in 120 consecutive patients undergoing LSG indicate that it is a safe and effective procedure for morbid obesity. However, long-term results are still pending.

Background Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors. Methods and Results Human normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size. Conclusions Our results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis.