Liat Sorski

Liat Sorski
Tel Aviv University | TAU · School of Psychological Sciences

Doctor of Philosophy

About

52
Publications
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1,078
Citations

Publications

Publications (52)
Article
Full-text available
Background The perioperative period often involves stress responses and surgery-induced hypothermia, which were suggested to hinder anti-metastatic immunity and promote cancer metastasis. During this critical period, immunotherapies are rarely used, given contraindications to surgery. However, recent pre-clinical studies support the feasibility of...
Article
Full-text available
Tumor excision is a necessary life-saving procedure in most solid cancers. However, surgery and the days before and following it, known as the immediate perioperative period (IPP), entail numerous prometastatic processes, including the suppression of antimetastatic immunity and direct stimulation of minimal residual disease (MRD). Thus, the IPP is...
Article
Full-text available
Type 2 diabetic mellitus (T2DM) is a common chronic disease and a substantial risk factor of other fatal illnesses. At its core is insulin resistance, where chronic low-level inflammation is among its main causes. Thus, it is crucial to modulate this inflammation. This review paper provides scientific neuroimmunological evidence on the protective r...
Article
Full-text available
The notion that stress and cancer are interlinked has dominated lay discourse for decades. More recent animal studies indicate that stress can substantially facilitate cancer progression through modulating most hallmarks of cancer, and molecular and systemic mechanisms mediating these effects have been elucidated. However, available clinical eviden...
Article
Full-text available
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-231HM human brea...
Article
Full-text available
Following excision of colorectal tumors, metastatic disease is prevalent, primarily occurs in the liver, and is highly predictive of poor prognosis. The perioperative period is now recognized as critical in determining the incidence of postoperative metastases and long-term cancer outcomes. Thus, various perioperative prophylactic interventions are...
Preprint
Full-text available
Numerous case studies have reported spontaneous regression of recognized metastases following primary tumor (PT) excision, but underlying mechanisms are elusive. Here we present a model of metastases regression and latency following PT excision, and identify potential underlying mechanisms. Using MDA-MB-231HM human breast cancer cells that express...
Article
The perioperative period holds disproportionate impact on long-term cancer outcomes. Nevertheless, perioperative interventions to improve long-term cancer outcomes are not clinical routines, including perioperative stress-reducing or immune-stimulating approaches. Here, mimicking the clinical setting of pre-operative distress, followed by surgery,...
Article
Full-text available
Background: Perioperative strategies can significantly influence long-term cancer outcomes. Dexmedetomidine, an α2-adrenoceptor agonist, is increasingly used perioperatively for its sedative, analgesic, anxiolytic, and sympatholytic effects. Such actions might attenuate the perioperative promotion of metastases, but other findings suggest opposite...
Article
It is assumed that following complete bilateral adrenalectomy, no adrenal tissue will re-develop, and adrenal hormone levels would remain low and unaffected by stress. However, anecdotal observations in animals and in patients suggest that under some unknown circumstances the opposite can occur. Herein we studied whether adrenalectomized rats can d...
Article
Marginating-hepatic (MH) leukocytes (leukocytes adhering to the sinusoids of the liver), were shown to exhibit unique composition and characteristics compared to leukocytes of other immune compartments. Specifically, evidence suggests a distinct pro- and anti-inflammatory profile of the MH-leukocyte population and higher cytotoxicity of liver-speci...
Article
Liver metastases are a major cause of colorectal cancer death, and the perioperative period is believed to critically affect the metastatic process. Here we tested whether blocking excess release of catecholamines and prostaglandins during surgical procedures of different extent can reduce experimental liver metastasis of the syngeneic CT26 colon c...
Article
Marginating-pulmonary (MP) leukocytes are leukocytes that adhere to the inner endothelium of the lung capillaries. MP-leukocytes were shown to exhibit unique composition and characteristics compared to leukocytes of other immune compartments. Evidence suggests higher cytotoxicity of natural killer cells, and a distinct pro- and anti-inflammatory pr...
Article
Full-text available
We recently reported that immune stimulation can be compromised if animals are simultaneously subjected to stressful conditions. To test the generalizability of these findings, and to elucidate neuroendocrine mediating mechanisms, we herein employed CpG-C, a novel TLR-9 immune-stimulating agent. Animals were subjected to ongoing stress (20-h of wet...
Article
Full-text available
The use of TLR agonists as an anti-cancer treatment is gaining momentum given their capacity to activate various host cellular responses through the secretion of inflammatory cytokines and type-I interferons. It is now also recognized that the perioperative period is a window of opportunity for various interventions aiming at reducing the risk of c...
Article
Dexmedetomidine is a widely used sedative, which activates alpha-2 adrenoceptors and exerts analgesic, sympatholytic, and anxiolytic effects. Surgery and the perioperative period are known to promote cancer progression. Different surgical routines and anaesthetic techniques were shown to considerably impact cancer recurrence rates. Studies of the p...
Article
Liver metastases are a major cause of cancer-related mortality. Marginating-hepatic (MH)-NK cells are strategically located in the liver sinusoids to physically interact and lyse circulating tumor cells. In cancer patients, the short peri-operative period is now recognized as critical in determining the progression of remaining malignant disease in...
Article
Full-text available
In vitro and ex-vivostudies assessing the impact of stress hormones on immune competence commonly replace the natural milieu of leukocytes with an artificial medium, excluding plasma factors, hormones, and cytokines. Given prevalent inconsistencies between in vitro, ex-vivo, and in vivo findings, we studied whether such procedures could yield misle...
Article
Full-text available
Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors...
Article
Extensive oncological surgeries were previously suggested to increase cancer recurrence rates. We herein studied the impact of different surgical procedures and sex on colorectal cancer liver metastasis, employing several tumor inoculation approaches in BALB/c mice. Experimental hepatic metastases of the syngeneic CT26 colorectal cancer line were i...
Article
Full-text available
To test whether marginating-pulmonary (MP) leukocytes in mice have a unique potential to identify and destroy aberrant circulating cells, we compared MP to circulating leukocytes with respect to natural killer (NK) cytotoxicity, proinflammatory characteristics, molecular determinants of activation, and response to IL-12 immunostimulation. Cytotoxic...
Article
In vitro studies assessing the impact of stress factors on immune competence employ “washed” leukocytes incubated in artificial media (e.g., PBMC in RPMI-1640), not reflecting the potential modulating impact of plasma factors on such effects, and deviating from the in vivo conditions where stress effects should ideally be studied. Therefore, here w...
Article
In vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, these findings are insufficient to conclude regarding the impact of endogenous release of these factors on in vivolevels of NKCC. Here we...
Article
Pro/anti-inflammatory cytokines are key players in the etiology of several diseases and in immune activation, and stress hormones were reported to modulate their levels. Our recent studies identified unique leukocyte populations that kill autologous tumor cells which are considered “immune-resistant”. These include marginating leukocytes residing i...
Article
Glucopyranosyl lipid adjuvant (GLA) is a newly developed FDA-approved synthetic TLR-4 agonist, differing from LPS by having a defined number, length, and position of carbon chains, resulting in an efficient Th1 activation with minimal adverse Th2 effects. GLA is currently studied clinically as a vaccine-adjuvant, and here, for the first time, we ex...
Article
Full-text available
Objective: Young adults often encounter sleep deprivation and stressful events. Both have been separately reported to modulate immunity, and occasionally they occur simultaneously. We assessed the combined effects of these conditions on immune competence in healthy students. Methods: Twenty-three participants (mean age 24 years; SD 1.86; 14 fema...
Article
Full-text available
Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus,...
Article
Immune stimulation therapy (IST) is gaining momentum along the last decade. Improved agents, including CpG-C, have been recently developed, and were shown to efficiently “shift” the immune system towards a pro-inflammatory state, while causing minimal adverse effects. Our recent studies suggested that stress can jeopardize the efficacy of immune-st...
Article
We recently reported that various stress paradigms suppress plasma IL-12 levels. The aim of this study was to elucidate potential neuroendocrine mediating mechanisms. Administration of prostaglandin-E2, epinephrine, and corticosterone, significantly reduced plasma IL-12 levels. However, when subjecting animals to stress or surgery, only the glucoco...
Article
Pro-(e.g., IL-12) and anti-inflammatory (e.g., IL-10) cytokines are believed to activate opposite responses and to be mutually inhibitory. The immunostimulatory agent CpG-C induces the production of IL-12, which activates NK cells. In the current study we tested the impact of CpG-C in conjunction with anti-IL-10 administration, conducting both in v...
Article
Interleukin-12 (IL-12) is a major pro-inflammatory cytokine, which promotes cell-mediated immunity and T(H)1 differentiation. In vitro studies indicated suppression of IL-12 production by several stress-related factors, but no effects of behavioral stress were shown on plasma IL-12 levels. Therefore, in the current study we (i) examined the in vivo...
Article
Full-text available
COX inhibitors and β-adrenergic blockers were recently shown to reduce cancer progression in animal models through various mechanisms. These include the prevention of immune suppression during the critical perioperative period, and the preclusion of direct promoting effects of catecholamines and prostaglandins on malignant tissue growth. To assess...
Article
Full-text available
Immune stimulation by biological response modifiers is a common approach in tumor immunotherapy. IL-12 was found effective in various animal studies, but clinical trials showed limited success. However, among other differences, animal models do not simulate psychological or physiological stress while employing IL-12, whereas cancer patients often e...
Article
Full-text available
Surgical procedures, including primary tumor resection, have been suggested to suppress immune competence and to promote postoperative infections and cancer metastasis. Catecholamines and prostaglandins were recently implicated in these processes, and in directly promoting tumor angiogenesis and invasion. To examine the integration of 2 complementa...
Article
Full-text available
Bi-directional influences between stress hormones and immune responses have been repeatedly documented, however, in the clinical setting they are rarely considered when immunotherapeutic approaches are used or studied in patients. As some immunotherapeutic treatments have shown great potential in animal models but have had limited success in patien...

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