hPL: physiologic and pathophysiologic observations.

Journal ArticleSerum human placental lactogen (hPL) levels were studied in 806 women in late pregnancy. The hPL levels were positively correlated with birth weight but were unrelated to maternal age, parity, socioeconomic status, or the sex of the newborn. The hPL levels peaked at 37 weeks' gestation and then declined moderately. An individual's hPL levels in late pregnancy are quite constant week to week. Patients with severe chronic hypertension have low hPL values; those carrying twins have high values

Human placental lactogen: a predictor of perinatal outcome?

Journal ArticleSerial human placental lactogen (hPL) determinations were performed on 806 women with normal and abnormal pregnancies late in the pregnancy. These results were not reported to the clinicians involved. For the study population as a whole, low hPL levels did not effectively predict those adverse perinatal outcome variables evaluated. Further analysis revealed that this was true both for the normal and abnormal pregnancy groups. Our data do not support the routine use of antepartum hPL screening, as advocated by others, as a means of improving perinatal outcome. In certain at-risk patients, there was an association between low hPL values and the presence of 1 or more of the adverse outcome variables. However, these patients had been recognized clinically as having fetuses in jeopardy

Characteristics of local and system immunity, and features of cancer stem cells in patients with different stage, dynamics and prognosis of colorectal carcinoma

Clinical prognosis in malignant tumors` is among the most challenging problems of contemporary medicine. It is thought to depend on both biologic properties of tumor cells and patients` immune status. The features of tumor cells and immune reactions are closely interrelated and mutually conditioned. Therefore, possible application of their characteristics as prognostic markers is of great fundamental and clinical importance. The aim of our study is to find out the most significant immune factors for prognosis of colorectal cancer (CRC) based on estimation of local and system immune factors, and some characteristics of tumor cells in the patients at various stages of the disease and different clinical course. Cellular factors of immunity and cytokines were studied in blood and tumor tissue of 299 patients with colorectal cancer (stages I-IV). Malignant cells expressing stem cell markers CSC), MHC and PDL-1 molecules were also counted in the tumor tissue. Blood samples were drawn prior to operation, and tissue samples were taken during surgery being the 1st line of treatment. Flow cytometry techniques (FCM), immunohistochemistry (IHC), and ELISA approach were employed. We have compared data on the patients at different CRC stages (with or without local and distant metastases), as well as cases with different course of the disease (evolving distant metastases and fatal outcome during period of observation). Our results demonstrated increased amounts of NK-cells and IL-6 concentration, along with decreased percentage of blood CD4+ cells in the patients with local metastases, as well as higher CSC numbers in malignant tissue. The initially generalized CRC cases with distant metastases were characterized by high levels of blood IL-6, monocytes and granulocytes responding to fMLF, while in tumor tissue elevated amounts of NKT, CSC and decreased expression of MHC and PDL-1 were observed on tumor cells, like as lower PD-1/ PDL-1 expression on tumor-infiltrating lymhocytes. Unfavorable CRC dynamics, i.e., metastasizing during the observation period was preceded by increased levels of IL-10 in blood, NK cells with poor cytotoxicity, monocytes and granulocytes responding to fMLF. In tumor tissue, overexpression of CSC markers and hypo-expression of MHC on tumor cells were noted. Fatal outcome was preceded by elevation of blood IL-6levels, tissue levels of NKТ and CSC percentages, along with decreased NK cells subset (CD16dimCD56bright) in blood, and decline of MHC-expressing cells in the tumor. Thus, high blood levels of IL-6 and IL-10, fMLF-responding monocytes and granulocytes, as well as elevated amounts of NKT and CSC, hypo-expression of MHC in tumor tissue could be considered prognostic markers of unfavorable course in CRC patients. Decrease of PD-1/PDL-1 expression on tumor cells and lymphocytes from its microenvironment in advanced CRC is of special attention, because checkpoint inhibitors are prescribed in such cases

Achievements and prospects of cellular technologies based on the activated lymphocytes in the treatment of malignant tumors

This article reviews the immune system and its role in the relationship between the tumor and the body of a patient with tumor diseases. It is about controlling homeostasis by recognizing and eliminating genetically alien substances (antigens). Antitumor treatment is now not only considered as an “instrument” for eliminating and destroying tumor cells, but also its ability to change/restore impaired functions of the immune system attracts attention. The used antitumor treatment is widely known to be immunosuppressive, stress and radiation effects also cause and/or enhance immunosuppression. In this work, the authors provide literature data demonstrating current status and problems of cellular immunotherapy of malignant tumors with the use of activated lymphocytes, and the role of antigen-specific T-lymphocytes as one of its most important agents is reviewed. Currently, among the immunotherapeutic methods, a special place is occupied by approaches involving the use of autologous or allogenic ex vivo stimulated immunocompetent cells (adoptive immunotherapy). The importance of complex influence on various links (T-, B-, NK-cell) and stages (presentation, recognition, proliferation, differentiation, migration, activation, effector functions) of the immune response is considered. The emergence of targeted drugs based on antibodies, as well as vaccines, especially dendritic cells, has provoked the emergence of a new wave of interest in the formation of specific antitumoral immune response mediated by T lymphocytes, so the introduction of the latter can be classified as a kind of targeted therapy. The value of antigen-specific T-lymphocytes in the formation of antitumor immunity is shown, which emphasizes the importance not only of CD8+, but also of CD4+ T-lymphocytes. In addition, there are suggestions of the possible significance of both T- and B-cells for developing a strategy of cellular immunotherapy. The literature data suggest that not only cytotoxic lymphocytes, but also T-helpers and even B-lymphocytes can be effective as antigen-specific lymphocytes as a component of antitumor treatment. The authors consider the possibility of obtaining antigen-specific T cells, as well as their further storage. The possibility of elimination or selective inhibition of regulatory T-cells during adoptive immunotherapy aimed at removing the suppressor effect on cytotoxic lymphocytes is studied. Various strategies for the use of cell therapy are also discussed

The International Society for Children's Health and the Environment Commits to Reduce Its Carbon Footprint to Safeguard Children's Health.

The Lancet Countdown and the 2018 Intergovernmental Panel on Climate Change declared that the worst impacts of climate change are and will continue to be felt disproportionately by children. Children are uniquely vulnerable to the consequences of climate change, including heat stress, food scarcity, increases in pollution and vector-borne diseases, lost family income, displacement, and the trauma of living through a climate-related disaster. These stressors can result in long-lasting physical and mental health sequelae. Based upon these concerns associated with climate change, the International Society for Children's Health and the Environment developed a statement about ways in which the Society could take action to reduce its contribution of greenhouse gas emissions. The objective of this article is to report our Society's plans in hopes that we may stimulate other scientific societies to take action. https://doi.org/10.1289/EHP6578

Expression level of androgen receptors in tumor tissue and its prognostic significance in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women

Aim. To evaluate the expression level and prognostic significance of androgen in primary operable luminal breast cancer without overexpression of Her2/neu in postmenopausal women. Methods. We analyzed treatment outcomes of 60 cases of primary operable (T1-2N0M0) luminal breast cancer without overexpression of Her2/neu in postmenopausal women. The follow-up period was 5 years. All cases were divided by immunohistochemical method into luminal A (20 females) and luminal B (40 patients) subtypes. Along with the standard panel of immunohistochemical markers, expression of nuclear androgen receptors was measured in tumor tissues of all patients. Depending on the expression levels, patients with luminal A and B subtypes were divided into three groups: (1) with high, (2) moderate and (3) low or negative expression. Results. Mean levels of androgen receptor expression in the nuclei of tumor cells in patients with luminal A subtype (57.3±5.9%) were higher than those of luminal B subtype (21.4±4.04%) by 62.7% (Mann-Whitney test, р=0.0026). In patients with luminal A subtype, the maximal accumulation of androgen receptors in the nuclei of tumor cells was 2.7 times higher (р=0.0023) than in patients with luminal B subtype. All cases diagnosed with the disease progression were characterized by low or negative level of nuclear androgen receptor expression. Conclusion. Negative and low levels of androgen receptor expression in tumor tissues of postmenopausal patients with luminal primary operable breast cancer without overexpression of Her2/neu might be an independent factor associated with poor prognosis

Варианты создания гетеротопических и ортотопических PDX-моделей колоректального рака человека

Aim. To create heterotopic and orthotopic patient-derived xenograft (PDX) models of colorectal cancer (CRC) by transplantation of patient’s tumor samples into immunodeficient BALB / c Nude mice.Materials and methods. The study was performed on 15 female BALB / c Nude mice aged 6–8 weeks weighing 21–25 g. All animals underwent transplantation of the tumor material obtained from CRC patients into the following sites: heterotopic transplantation (under the skin of the thigh and into the omentum), orthotopic transplantation (into the descending and ascending colon and into the cecum). Weight and general condition of the animals and the size of the tumor nodule had been monitored for 80 days. The success of each model was assessed by the degree of engraftment, the dynamics of tumor growth, and the reproducibility of histopathologic characteristics. At the end of the experiment, the animals were euthanized by cervical dislocation.Results. 100% survival of the animals and similar tumor growth dynamics in the xenograft models were observed throughout the experiment. The analysis of histologic specimens obtained from the xenografts and patient’s tumor showed their correspondence to moderately differentiated intestinal adenocarcinoma. The main advantages and disadvantages of different variants of PDX models were described.Conclusion. Heterotopic and orthotopic PDX models reproduce the morpho-histologic characteristics of human tumors and demonstrate stable growth dynamics. Therefore, they are a suitable tool for the development, testing, and validation of potential anticancer drugs.Цель. Создание гетеротопических и ортотопических моделей ксенографтов колоректального рака (КРР), полученных от пациентов (Patient-derived xenograft, PDX-модель), путем трансплантации образцов опухоли пациента иммунодефицитным мышам линии Balb/c nude.Материалы и методы. Проведено исследование на 15 самках мышей линии Balb/c nude, возраст 6–8 нед, масса тела 21–25 г. Всем животным проведена трансплантация опухолевого материала, взятого от пациентов с КРР, в следующие сайты: гетеротопические (под кожу бедра, в сальник); ортотопические (в нисходящий и восходящий отделы толстой кишки, в слепую кишку). В течение 80 сут у животных контролировали следующие параметры: массу тела, общее состояние, объем опухолевого узла. Успешность каждой из моделей оценивали по степени приживления, динамике опухолевого роста и воспроизводимости гистопатологических характеристик. По завершению эксперимента животным выполнена эвтаназия методом цервикальной дислокации.Результаты. На протяжении всего эксперимента наблюдалась 100%-я выживаемость животных и схожая динамика роста ксенографтов. Анализ гистологических препаратов ксенографтов и опухоли пациентов показал их соответствие умеренно дифференцированной аденокарциноме кишки. Описаны основные преимущества и недостатки создания различных вариантов PDX-моделей.Заключение. Гетеротопические и ортотопические PDX-модели воспроизводят морфогистологические признаки человеческой опухоли и обладают устойчивой динамикой роста, следовательно, являются подходящим инструментом для разработки, тестирования и валидации потенциальных лекарственных препаратов против рака

Вирус болезни Ньюкасла и иммунитет - эффективный альянс в борьбе против рака (обзор литературы)

Cancer is still the leading cause of death in developed countries. Oncolytic virus (OV) therapy is a promising new strategy for tumor growth inhibition. Despite the fact that the oncolytic function of some viruses was discovered in the last century, it has not been properly applied and recognized. The viruses of the Paramyxoviridae family, particularly Newcastle disease virus (NDV), are powerful oncolytic and immunostimulating agents non-pathogenic in humans. NDV is characterized by a selective infection and spread of the virus in tumor cells, direct cytopathic effect, and indirect induction of the innate and adaptive immune system of the host. However, intratumoral administration of OVs is not always possible and results in only local effect. There is an assumption that immune system cells can be used as possible carriers of OVs to provide temporary protection against immune system factors of the body. Dendritic cells (DCs) were the most effective cellular carriers among numerous types of immune cells evaluated in studies of the OV effect. In conclusion, the authors suggest that the use of OVs as an adjuvant for tumor antigens in the development and improvement of DC vaccine optimizes the development of antitumor immune response, STAT - signal transducer and activator of transcription.В настоящее время рак остается одной из ведущих причин смертности в развитых странах мира. Использование онколитических вирусов (ОВ) является перспективным возможным методом ингибирования опухолевого роста. Несмотря на то, что открытие онколитической функции ряда вирусов произошло еще в прошлом веке, использование ОВ до сих пор не нашло должного признания. Одни из наиболее многообещающих - вирусы семейства Paramyxoviridae, в частности вирус болезни Ньюкасла (ВБН), не являющийся патогенным для человека и обладающий некоторыми эффективными механизмами воздействия на опухолевые клетки и индукции иммунного ответа. Для ВБН характерны селективное инфицирование и распространение вируса в опухолевых клетках, прямой цитопатический эффект, а также косвенная индукция врожденного и адаптивного иммунного ответа хозяина. Однако внутриопухолевое введение ОВ не всегда является возможным и приводит лишь к локальному действию. Существует предположение, что клетки иммунной системы могут использоваться в качестве возможных носителей ОВ для обеспечения временной защиты от факторов иммунной системы организма опухоленосителя. В исследованиях действия ОВ самыми эффективными клеточными носителями среди многочисленных оцениваемых типов иммунных клеток являлись дендритные клетки (ДК). Таким образом, совместное действие ОВ и ДКВ является важным для взаимного потенцирования противоопухолевого эффекта обоих компонентов (вирусного и клеточного); получение таких продуктов представляется целесообразным с целью их дальнейшего клинического применения

Comparative analysis of some immunological parameters depending on the tumor location on the right and left sides of colon

Background: Colorectal cancer is now an urgent problem in oncology. Recently, specialists have been interested in a comparative analysis of differences in the clinical course of malignant tumors in the proximal and distal colon. The sections differ not only in their embryogenesis and sources of blood supply, but also in the clinical course and population and epidemiological characteristics. The issue of distinctive immunological characteristics of tumors of the colon depending on the location remains open.Objective: A comparative analysis of local subpopulations of immunocompetent cells and an assessment of number of cells with the CD45+/- phenotype expressing toll-like receptors (TLRs) depending on the tumor location on the right or left sides of the colon.Material and methods: The study included 50 patients with verified colon cancer. The majority of patients were females – 26 (52%), aged 67 ± 0.4 years, and 50% of patients with stage II disease. Depending on the tumor location (the right or left sides of the colon), the patients were divided into 2 groups of 25 people each. All patients underwent standard surgery at the initial stage. The obtained material was used for subsequent studies: a cell suspension was obtained from a tumor tissue fragment, the perifocal zone (1–3 cm from the tumor) which was processed using an antibody panel (Becton Dickinson, USA) to identify the main subpopulations of leukocytes and lymphocytes. Expression of TLRs (2, 3, 4, 8, 9) on CD45+, CD45- cell populations was also determined using the BD FACSCanto flow cytometer (Becton Dickinson, USA). Statistical processing of the results was performed using the STATISTICA 13.3 package (StatSoft Inc., USA).Results: A comparative analysis of immunological parameters, depending on the tumor location on the right or left sides of the colon, showed:Tissues of the right-sided tumors had a higher T-lymphocytic infiltration, compared to the left-sided tumors, while the latter showed a higher B-lymphocytic infiltration (p = 0.025).Peritumoral zone tissues of left-sided tumors demonstrated a decrease of lymphocytes levels (p = 0.027), NKT – (p = 0.035), NK – (p = 0.041) and В lymphocytes (p = 0.038), and a significant increase in CD8+- (p = 0.02) and DP cells (p = 0.0018).Left-sided tumors showed a percentage decrease of CD45- cells expressing TLR4 and TLR8, compared to right-sided tumors, by 38% (p = 0.038) and 25% (p = 0.043).There was a decrease in the number of CD45+ cells expressing TLR2 and TLR4 in left-sided tumors by 54% (p = 0.035) and 33% (p = 0.04) respectively, than in right-sided tumors.The percent of CD45- cells expressing TLR4 in the perifocal tissues of left-sided tumors decreased by 61% (p = 0.031) in comparison to the corresponding tissues in right-sided tumors.The numbers of CD45+ cells expressing TLR2 and TLR4 were 81% (p = 0.02) and 87% (p = 0.018) lower respectively in the peritumoral tissues of left-sided tumors, compared to the corresponding tissues in right-sided tumors.Conclusion: The revealed characteristics of the local subpopulations of immunocompetent cells and the numbers of CD45+/- cells expressing TLRs depending on the tumor location on the right or left sides of the colon can serve as a prognosis of the disease clinical course and the choice of further treatment tactics