Thyroid Cancer in Regions Most Contaminated after the Chernobyl Disaster.

Exposure to ionizing radiation, especially during childhood, is a well-established risk factor for thyroid cancer. Following the 1986 Chernobyl nuclear power plant accident the total number of cases of thyroid cancer registered between 1991 and 2015 in males and females who were less than 18 years old exceeded 19,000 (in Belarus and Ukraine, and in the most contaminated oblasts of the Russian Federation). However, as indicated by the United Nations Scientific Committee on the Effects of Atomic Radiation the fraction of the incidence of thyroid cancer attributable to radiation exposure among the non-evacuated residents of the contaminated regions of Belarus, Ukraine and Russia is of the order of 0.25. Apparently, the increased registration of thyroid neoplasms in the parts of these countries is a classical 'screening effect', i.e., massive diagnostic examinations of the risk-aware populations performed with modern eqipment resulting in detection of many occult neoplasms (incidentalomas). Moreover, one type of thyroid cancer previously called 'encapsulated follicular variant of papillary thyroid carcinoma' is non-invasive and instead of 'carcinoma' should now be recognized as 'noninvasive follicular thyroid neoplasm with papillary-like nuclear features.' Other potential causes of overdiagnosing of thyroid tumors include increase of the spontaneous incidence rate of this disease with age, iodine deficiency among children from Belarus, Russia and Ukraine, and/or consumption by these children of drinking water containing high levels of nitrates that likely coincides with the carcinogenic effect of radiation on the thyroid gland.

The effect of pre-emptive oral pregabalin on opioid consumption in patients undergoing laparoscopic sleeve gastrectomy with an analysis of intraoperative hemodynamic stability and quality of recovery: study protocol for a randomized, prospective, double-blind study.

BACKGROUND: Obese patients undergoing laparoscopic sleeve gastrectomy (LSG) are particularly at risk of opioid-related side effects. To reduce patient exposure to opioids, multimodal analgesia, which involves the use of drugs of different classes, may be utilized. One of the drugs under consideration is pregabalin. Despite an opioid-sparing potential, few studies assess the role of pregabalin as an element of multimodal analgesia in LSG. Considering the limited number and inconsistent results of available studies, we decided to conduct a randomized, prospective study on the effect of preemptive pregabalin administration in obese patients on opioid consumption, pain scores, the incidence of opioid side effects, and hemodynamical stability. METHODS: The study is designed as a prospective randomized controlled trial with double-blinding. Randomization will be performed in a block with a parallel 1:1 allocation. The intervention will involve receiving a pregabalin 150 mg capsule 1-2 h before the surgery, whereas the control group will receive an identically looking placebo. The primary outcome measure will be total oxycodone consumption in the first 24 h following surgery. Secondary outcome measures will be pain severity assessed using the Numerical Rating Scale (NRS) 1, 6, 12, and 24 h after surgery, postoperative sedation on the Ramsay scale, PONV impact scale, the incidence of desaturation episodes < 94%, and episodes of blurred vision at 1, 6, 12, and 24 h after surgery, intraoperative hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), total fluid volume, and total ephedrine dose. Patient comfort will be additionally assessed using the QoR-40 questionnaire at discharge. DISCUSSION: The study will explore the efficacy and safety of preemptive pregabalin in a dose of 150 mg as a co-analgesic used in multimodal analgesia for LSG. As studies on opioid-sparing regimes concern the safety of obese patients, we aim to contribute objective data with a relatively large study sample size. The result of the present clinical trial may support the reassessment of recommendations to use pregabalin in the studied population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05804591. Registered on 07.04.2023.

Successful Anesthetic Management for Obese Patients with Interstitial Lung Disease Undergoing Laparoscopic Sleeve Gastrectomy: A Bridge to Improved Lung Transplant Eligibility.

BACKGROUND Patients with obesity with interstitial lung diseases (ILD) are encouraged to lose weight, as it improves lung function and lung transplant eligibility. As exercise tolerance in these patients is low and weight gain is a common adverse effect of corticosteroids, bariatric surgery can be an effective method for the management of obesity in this patient group. However, perioperative complications in such high-risk patients remain a concern. Therefore, we aimed to demonstrate successful anesthetic management for obese patients with ILD, which may be practically utilized to reduce perioperative pulmonary complications and improve outcomes. CASE REPORT Our case report presents a 42-year-old man with ILD who underwent laparoscopic sleeve gastrectomy (LSG). Preoperative studies revealed severe restrictive disease, right ventricular overload with assessed intermediate risk of pulmonary hypertension, and heart failure, with preserved left ventricle fraction but with poor exercise tolerance. Patient had opioid-free anesthesia (OFA) and postoperative multimodal analgesia. Following a 24-h stay in the Post-Anesthesia Care Unit, the patient was transferred to the ward and ultimately discharged home 2 days thereafter. At the 1-year follow-up, the patient reduced his weight by 40 kg and reported a significant improvement in physical capacity. CONCLUSIONS Our record demonstrates that OFA can be successfully used in high-risk patients with ILD undergoing LSG. In a period of a year, the patient improved so much that he no longer required lung transplantation, which may encourage clinicians to provide bariatric surgery using the OFA technique in the population of patients with obesity and severe respiratory illness.

Effect of Intramuscular Tramadol on the Duration of Clinically Relevant Sciatic Nerve Blockade in Patients Undergoing Calcaneal Fracture Fixation: A Randomized Controlled Trial.

BACKGROUND: Calcaneal fracture fixation can generate severe postoperative pain and analgesia can be supported by a sciatic nerve block. However, following resolution of the sensory blockade, rebound pain may ensue. The aim of this study was to assess whether an incidental finding of two patients with an extension of the sciatic nerve block beyond 24 h following 100 mg of intramuscular tramadol administration could be confirmed. METHODS: Thirty-seven patients scheduled for a calcaneal intramedullary fixation (Calcanail®) were randomly divided into two groups. The tramadol group (n = 19) received a sciatic nerve block with 20 mL of 0.25% bupivacaine and a concomitant dose of 100 mg of intramuscular tramadol, while the control group (n = 18) received an identical sciatic nerve block with concomitant injection of normal saline (placebo). All patients had a spinal anesthesia with light sedation for the procedure. The time to first analgesic request defined as appearance of any pain (NRS > 0) was assessed as the primary endpoint with a clinically relevant expected result of at least 50% elongation in sensory blockade. RESULTS: The median time to first analgesic request from time of blockade in the tramadol group was 670 min compared with 578 min in the control group. The result was clinically not relevant and statistically not significant (p = 0.17). No statistical difference could be demonstrated in the time to first opioid request, although a trend for opioid sparing in the tramadol group could be seen. Total morphine consumption in the first 24 h was also statistically insignificant (the tramadol group 0.066 mg kg-1 compared with 0.125 mg kg-1 in the control group). In conclusion, intramuscular tramadol does not extend the duration of analgesia of a sciatic nerve block following a calcaneal fracture fixation beyond 2 h and an opioid sparing effect could not be demonstrated in this trial.

Efficacy and Side Effect Profile of Intrathecal Morphine versus Distal Femoral Triangle Nerve Block for Analgesia following Total Knee Arthroplasty: A Randomized Trial.

(1) Background: The management of postoperative pain after knee replacement is an important clinical problem. The best results in the treatment of postoperative pain are obtained using multimodal therapy principles. Intrathecal morphine (ITM) and single-shot femoral nerve block (SSFNB) are practiced in the treatment of postoperative pain after knee replacement, with the most optimal methods still under debate. The aim of this study was to compare the analgesic efficacy with special consideration of selected side effects of both methods. (2) Materials and methods: Fifty-two consecutive patients undergoing knee arthroplasty surgery at the Department of Orthopedics and Traumatology of the Medical University of Warsaw were included in the study. Patients were randomly allocated to one of two groups. In the ITM group, 100 micrograms of intrathecal morphine were used, and in the SSFNB group, a femoral nerve block in the distal femoral triangle was used as postoperative analgesia. The other elements of anesthesia and surgery did not differ between the groups. (3) Results: The total dose of morphine administered in the postoperative period and the effectiveness of pain management did not differ significantly between the groups (cumulative median morphine dose in 24 h in the ITM group 31 mg vs. SSFNB group 29 mg). The incidence of nausea and pruritus in the postoperative period differed significantly in favor of patients treated with a femoral nerve block. (4) Conclusions: Although intrathecal administration of morphine is similarly effective in the treatment of pain after knee replacement surgery as a single femoral triangle nerve block, it is associated with a higher incidence of cumbersome side effects, primarily nausea and pruritus.

Marie and Irène Curie, two brilliant women who pioneered the development of nuclear chemistry, radiotherapy, and radiobiology.

OBJECTIVE: To describe the contributions of Marie Sklodowska-Curie and her daughter Irene Curie to radiation science and how these studies in physics, chemistry and medicine led to the need to study radiobiological effects. CONCLUSIONS: The seminal discoveries of Maria Sklodowska-Curie in radiation physics and chemistry provided the basis for later investigations of the effects of ionizing radiation on cells and tissues and the role of radioactivity in mutagenesis and carcinogenesis. Both Maria and Irene contributed to the development of radiotherapy and the use of x-rays and radioisotopes in medical diagnosis. Their legacy is not confined to their own generation but can be traced through grand- and great-grand-students of these pioneering women.

Effect of Bilateral Quadratus Lumborum Block Type I on Patient Satisfaction and Incidence of Chronic Postsurgical Pain Following Cesarean Section-A Randomized Controlled Trial.

BACKGROUND: Quadratus lumborum block (QLB) provides a reduction in pain scores and opioid consumption after cesarean section (CS). Intrathecal morphine (ITM) is still considered as the gold standard of acute postoperative pain therapy, but it does have some significant side effects. The aim of this clinical study was to evaluate whether performing the quadratus lumborum block type I in patients undergoing CS would be associated with an increased satisfaction of pain therapy and a decreased incidence of chronic postsurgical pain (CPSP). METHODS: Sixty patients scheduled for elective CS were enrolled. All patients received spinal anesthesia and were randomly allocated to either the QLB group (received bilateral quadratus lumborum block type I with the use of 24 m mL 0.375% ropivacaine) or the control group (received no block). The level of satisfaction was evaluated using a three-step scale and the answers provided in a questionnaire regarding the patients' satisfaction with the method of postoperative pain treatment in the first 48 h. After a 6-month period, all patients were interviewed to evaluate the incidence and possible severity of CPSP. RESULTS: Satisfaction scores were significantly lower in the QLB group than in the control group (p = 0.0000). There were no significant differences between the QLB and control groups regarding the occurrence of chronic postsurgical pain after 6 months following CS (p = 0.102). No statistical differences between the groups were recorded when we compared the results of the questionnaire after a period of 48 h from CS (the number of participants were limited in number). CONCLUSIONS: QLB type I is an analgetic option that increased the satisfaction of parturients with pain therapy after CS compared to patients who did not receive the block, and there is a tendency for a lower incidence of CPSP.

Quadratus Lumborum and Transversus Abdominis Plane Blocks and Their Impact on Acute and Chronic Pain in Patients after Cesarean Section: A Randomized Controlled Study.

BACKGROUND: Severe postoperative pain is a significant problem after cesarean sections. METHODS: This study was a randomized, controlled trial of 105 patients conducted in two hospitals. All patients were anesthetized spinally for elective cesarean section. Each participant was randomly allocated to one of three study groups: the quadratus lumborum block (QLB) group, the transversus abdominis plane block (TAPB) group, or the control (CON) group. The primary outcome of this study determined acute pain intensity on the visual analog scale (VAS). The secondary outcomes determined morphine consumption and chronic pain evaluation according to the Neuropathic Pain Symptom Inventory (NPSI) after hospital discharge. RESULTS: At rest, the pain intensity was significantly higher in the CON group than in the QLB and TAPB groups at hours two and eight. Upon activity, the pain in the control subjects was more severe than in the QLB and TAPB groups in three and two of five measurements, respectively. Moreover, morphine consumption was significantly lower in the QLB (9 (5-10)) and TAPB (10 (6-14)) groups than in the CON (16 (11-19)) group. Persistent postoperative pain was significantly lower in the QLB group than in the CON group at months one and six following hospital discharge. CONCLUSIONS: Both the QLB and TAPB can improve pain management after cesarean delivery. Moreover, the QLB might reduce the severity of persistent postoperative pain months after cesarean section.

A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice.

Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. In the present study we demonstrate for the first time that 1-methyl nicotinamide (MNA), a derivative of vitamin B3, significantly (1.6 to 1.9 times) prolonged survival of BALB/c mice irradiated at LD30/30 (6.5 Gy), LD50/30 (7.0 Gy) or LD80/30 (7.5 Gy) of γ-rays when the MNA administration started as late as 7 days post irradiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B3 derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). These pro-survival effects did not seem to be mediated by stimulation of haematopoiesis, but might be related to anti-inflammatory and/or anti-thrombotic properties of the vitamin B3 derivatives. Our results show that MNA may represent a prototype of a radioremedial agent capable of mitigating the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of ionizing radiation.

Time to rejuvenate ultra-low dose whole-body radiotherapy of cancer.

The results of clinical trials performed from the 1930s until the end of the 20th century in which total-body ultra-low level ionizing radiation (TB-LLR) was used demonstrate that this form of treatment can be equal or superior to other systemic anti-neoplastic modalities in terms of the rates of remissions, toxicity, and side effects. In this review, we provide the rationale for TB-LLR and analyze the results of reliable clinical trials in patients with predominantly lymphoproliferative disorders but also advanced solid cancers. The doses used in these trials did not exceed 0.1-0.2 Gy per fraction and cumulative totals ranged from 1 to 4 Gy. Based on the reviewed results we conclude that it is appropriate to revive interest in and resume clinical investigations of TB-LLR in order to refine and improve the effectiveness of such treatment, whether employed alone or in combination with other anticancer strategies.

[Hypotension - a complication of subarachnoid anesthesia especially dangerous in patients aged]. / Hipotensja ­ powiklanie znieczulenia podpajeczynówkowego szczególnie grozne u chorych w podeszlym wieku.

Demographic data clearly show the progressive aging of societies. Problems and specificity of anaesthesia in the elderly becomes a particularly important issue in this context. Spinal anesthesia is a method often used to anesthetize elderly patients, and hypotension is one of its most common early complications. Untreated or improperly treated hypotension increases the risk of perioperative complications such as myocardial infarction, ischemic stroke or acute renal failure. The prevention of hypotension consists of intravenous fluid therapy and pre-emptive use of vasoconstrictor drugs. Among vasoconstrictors, ephedrine and phenylephrine are commonly used to treat hypotension due to spinal anaesthesia. Both drugs are available in Poland. Issues related to their use in the treatment of hypotension caused by spinal anaesthesia in the elderly, including the features of both drugs, their method of administration and dosage based on the literature and own experience are the subject of this study. It should be noted, however, that most studies in the use of ephedrine and phenylephrine as a targeted treatment for hypotension concern the obstetric patient population while the elderly population is underrepresented and the results are inconclusive.

Bringing Radiation Exposures and Associated Health Risks into Perspective-Development of an App.

The NATO HFM 291 research task group (RTG) on "Ionizing Radiation Bioeffects and Countermeasures" represents a group of scientists from military and civilian academic and scientific institutions primarily working in the field of radiobiology. Among other tasks, the RTG intends to extend their work on risk estimation and communication to bridge the gap in appropriate judgment of health risks given a certain radiation exposure. The group has no explicit psychological background but an expertise in radiobiology and risk assessment. The group believes that, as one of the essential first steps in risk communication, it is required to put radiation risk into perspective. Radiation risk requires a weight in comparison to already-known risks. What we envision is to Compare Radiation exposure-associated health Risks (CRRis App) with daily life health risks caused by other common exposures such as cigarette smoking, driving a car, etc. Within this paper, we provide (1) an overview of health risks after radiation exposure, (2) an explanation of the task and concept of an envisioned CRRis App, (3) an overview of existing software tools related to this issue, (4) a summary of inputs and discussions with experts in the field of radiation protection and risk communication during the ConRad conference, and finally, (5) identification of the next steps in the development of the App.

Transversus abdominis plane block versus quadratus lumborum block type 2 for analgesia in renal transplantation: A randomised trial.

BACKGROUND: Several studies have shown an analgesic efficacy of a transversus abdominis plane block (TAPB) in reducing opioid requirements during and after cadaveric renal transplantation surgery, but the effect of a quadratus lumborum block (QLB) in this type of surgery is unclear. OBJECTIVES: The main objective of this prospective, randomised, double-centre clinical study was to compare the analgesic efficacy of a one-sided lateral approach TAPB with a unilateral QLB type 2 in cadaveric renal transplantation surgery. DESIGN: Randomised, single-blinded trial. SETTING: Two University-affiliated tertiary care hospitals between April 2016 and May 2017. PATIENTS: A total of 101 patients aged more than 18 years, scheduled for cadaveric renal transplantation. INTERVENTIONS: On receiving ethical board approval and individual informed consent, consecutive patients were allocated randomly to receive either an ultrasound-guided single-shot lateral TAPB or an ultrasound-guided single-shot QLB type 2 on the surgical side using 20 ml of bupivacaine 0.25% with adrenaline after a standardised induction of general anaesthesia. All patients on surgical completion and recovery from general anaesthesia were admitted to the postanaesthesia care unit for 24 h. They received standardised intravenous patient-controlled analgesia with fentanyl, and their pain scores were noted at regular intervals. MAIN OUTCOME MEASURES: The primary endpoint was total cumulative fentanyl dose used per kg body mass in the first 24 h after surgery. Secondary outcomes were the need to start a continuous infusion of fentanyl in addition to patient-controlled analgesia boluses during the stay in post-anaesthesia care unit, postoperative pain severity measured using a numerical rating scale, patient satisfaction with analgesic treatment, evidence of postoperative nausea and vomiting, pruritus and sedation level. RESULTS: The 49 patients allocated to the QLB type 2 group used significantly less fentanyl per kg in the first 24 h after surgery than the 52 patients who received a TAPB (median [IQR] 4.2 [2.3 to 8.0] µg kg versus 6.7 [3.5 to 10.7] µg kg, P = 0.042). No statistically significant differences were noted in the secondary endpoints within the study, including the frequency of adverse effects of opioids. CONCLUSION: The reduction of fentanyl consumption in the first 24 h after renal transplantation with no difference in pain intensity and patient satisfaction shows a beneficial effect of one-sided QLB type 2 over a one-sided TAPB in regards to postoperative analgesia. However, the reduction in opioid consumption did not affect the frequency of opioid-related adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02783586.

How fast does wasp venom immunotherapy affect a regulatory T cell subpopulation (CD4+ CD25+ Foxp3+) and the synthesis of interleukins 10, 21 and transforming growth factor ß1?

INTRODUCTION: The literature describes the influence of venom immunotherapy (VIT) on the subpopulation of T regulatory cells (CD4+ CD25+ Foxp3+) and the synthesis of IL-10, TGF-ß1 as well as many other cytokines at various times after immunotherapy. AIM: To assess changes in the percentage of cells of CD4+ and CD25+ in peripheral blood and serum concentrations of IL-10, IL-21 and TGF-ß1 in the early stages of VIT. MATERIAL AND METHODS: The study included 18 patients who were allergic to wasp venom and who in the past underwent systemic anaphylactic reaction after stinging, meeting the criteria to qualify for VIT. The immunoenzymatic method (ELISA) was used to assess concentrations of cytokines IL-10, IL-21 and TGF-ß1 and the surface antigens CD4 and CD25 on the cells. The concentrations were determined by flow cytometry method at baseline (before VIT) and after 2.5 and 24 h from the VIT starting point. RESULTS: The mean values of the activity of T lymphocytes CD4+ CD25+ FoxP3+ and concentrations of the cytokines IL-10, IL-21 and TGF-ß1 are shown in table. CONCLUSIONS: A 24-hour activation assessment of serum concentrations of cytokines IL-10, IL-21 and TGF-ß1 during the first day of the Hymenoptera venom immunotherapy by ultra-rush protocol does not show the significant dynamics of change of the examined parameters.

Effect of internal contamination with tritiated water on the neoplastic colonies in the lungs, innate anti-tumour reactions, cytokine profile, and haematopoietic system in radioresistant and radiosensitive mice.

Tritium is a potentially significant source of internal radiation exposure which, at high levels, can be carcinogenic. We evaluated whether single intraperitoneal injection of BALB/c and C57BL/6 mice with tritiated water (HTO) leading to exposure to low (0.01 or 0.1 Gy) and intermediate (1.0 Gy) cumulative whole-body doses of ß radiation is immunosuppressive, as judged by enhancement of artificial tumour metastases, functioning of NK lymphocytes and macrophages, circulating cytokine's levels, and numbers of bone marrow, spleen, and peripheral blood cells. We demonstrate that internal contamination of radiosensitive BALB/c and radioresistant C57BL/6 mice with HTO at all the absorbed doses tested did not affect the development of neoplastic colonies in the lungs caused by intravenous injection of syngeneic cancer cells. However, internal exposure of BALB/c and C57BL/6 mice to 0.1 and 0.01 Gy of ß radiation, respectively, up-regulated cytotoxic activity of and IFN-γ synthesis in NK lymphocytes and boosted macrophage secretion of nitric oxide. Internal contamination with HTO did not affect the serum levels of pro- (IL-1ß, IL-2, IL-6, TNF-α,) and anti-inflammatory (IL-1Ra, IL-4, IL-10) cytokines. In addition, exposure of mice of both strains to low and intermediate doses from the tritium-emitted ß-particles did not result in any significant changes in the numbers of bone marrow, spleen, and peripheral blood cells. Overall, our data indicate that internal tritium contamination of both radiosensitive and radioresistant mice leading to low and intermediate absorbed ß-radiation doses is not immunosuppressive but may enhance some but not all components of anticancer immunity.

Iliac Fascia Compartment Block and Analgesic Consumption in Patients Operated on for Hip Fracture.

BACKGROUND: Fractures of the proximal femur in elderly patients are a challenge for orthopedics, anesthe-sio-logy and geriatrics. Early mobilization reduces postoperative mortality among these patients. Effective anal-gesia is necessary to achieve this goal. MATERIAL AND METHODS: A retrospective analysis of perioperative medical records of 78. patients undergoing surgical treatment of proximal femur fractures was performed. Group 1 (n=35)consisted of patients who were treated with pharmacologic analgesia only (systemic analgesics) and Group 2 (n=43) involved patients who re-ceived a preoperative fascia iliaca compartment block (FICB) and pharmacologic analgesia. FICB was per-formed under ultrasound guidance, and systemic analgesics were administered according to a standardized pro-to-col. Demographics, anesthesia and operation data as well as the dosage of analgesics used on postoperative day 0 were collected for the study. RESULTS: Patients with antecedent iliac fascia blockade required fewer analgesic interventions (3 vs. 11, p <0.0001) and showed significantly less need for analgesics than non-block patients. No complications were observed after performing FICB. CONCLUSION: The iliac fascia compartment block produces effective postoperative analgesia and reduces postoperative opioid consumption.

Cancer immunotherapy: how low-level ionizing radiation can play a key role.

The cancer immunoediting hypothesis assumes that the immune system guards the host against the incipient cancer, but also "edits" the immunogenicity of surviving neoplastic cells and supports remodeling of tumor microenvironment towards an immunosuppressive and pro-neoplastic state. Local irradiation of tumors during standard radiotherapy, by killing neoplastic cells and generating inflammation, stimulates anti-cancer immunity and/or partially reverses cancer-promoting immunosuppression. These effects are induced by moderate (0.1-2.0 Gy) or high (>2 Gy) doses of ionizing radiation which can also harm normal tissues, impede immune functions, and increase the risk of secondary neoplasms. In contrast, such complications do not occur with exposures to low doses (≤0.1 Gy for acute irradiation or ≤0.1 mGy/min dose rate for chronic exposures) of low-LET ionizing radiation. Furthermore, considerable evidence indicates that such low-level radiation (LLR) exposures retard the development of neoplasms in humans and experimental animals. Here, we review immunosuppressive mechanisms induced by growing tumors as well as immunomodulatory effects of LLR evidently or likely associated with cancer-inhibiting outcomes of such exposures. We also offer suggestions how LLR may restore and/or stimulate effective anti-tumor immunity during the more advanced stages of carcinogenesis. We postulate that, based on epidemiological and experimental data amassed over the last few decades, whole- or half-body irradiations with LLR should be systematically examined for its potential to be a viable immunotherapeutic treatment option for patients with systemic cancer.

TIMP4 expression is regulated by miR-200b-3p in prostate cancer cells.

In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA-200b-3p. The levels of TIMP4 and miR-200b-3p expression were determined by real time PCR in 27 prostate carcinomas and eight benign prostatic hyperplasia samples. We found that miR-200b-3p positively correlated with TIMP4 expression in cancer samples (r = 0.46; p < 0.02). Moreover, mean miR-200b-3p level and TIMP4 expression were both higher in cancer tissues compared to benign prostatic hyperplasia samples (p > 0.05). Next, to test probable mechanisms of the regulation androgen-sensitive human prostate adenocarcinoma cells (LNCaP) were transfected with synthetic-miR-200b-3p or its synthetic antagonist. Modulation of miR-200b-3p in LNCaP cells had an impact on TIMP4 expression confirming the observation made in analyzed clinical samples. Two targets of miR-200b-3p: ZEB1 and ETS1 were investigated subsequently as potential regulators of TIMP4, however, no effect of their modulation on TIMP4 expression in LNCaP cells was found. Concluding, miR-200b-3p mediates regulation of TIMP4 expression in prostate cancer but exact mechanism needs to be investigated.