Radiation therapy failure in prostate cancer patients: risk factors and methods of detection

Radiation therapy for clinically localized prostatic carcinoma remains one of the mainstays among therapeutic approaches; however, patients continue to fail radiation therapy at too high a rate. This article reviews the risk factors and methods of detection for prostate cancer recurrence. The relative merits of the three major pre-therapy prognostic indicators-TNM staging, Gleason score, and serum prostate-specific antigen (PSA) levels-are discussed. The use of staging and Gleason score, as well as digital rectal examination, transrectal ultrasound, and post-radiation prostate biopsies in detecting failure of radiation therapy is reviewed. Challenges relating to the use of serum PSA levels as an indicator of recurrence are examined. Finally, this article makes recommendations as to procedure for evaluating patients suspected of failing radiation therapy.     

Classification et aspects anatomopathologiques des tumeurs endocrines digestives

Gastrointestinal and pancreatic endocrine tumors GIPET are rare and represent only 2 % of malignant tumors. Beyond their common features, endocrine tumors are characterized by a marked diversity, which results from the large functional, structural and embryological heterogeneity of normal endocrine cells. Despite the rational basis for predicting prognosis provided by the WHO classification, there is no reliable means of predicting the clinical course of patients with gastrointestinal and pancreatic endocrine tumors. The current criteria used for the definition of the tumor grade remain unsatisfactory. According to the WHO classification system, pathologists vary significantly in their reporting of endocrine tumors. Recently, the European Neuroendocrine Tumour Society (ENETS) has proposed a TNM (tumor–node–metastasis) classification for gastrointestinal and pancreatic endocrine tumors. The use of this classification is considered simple and valuable. It is hoped that the combination of WHO classification, with anatomical staging systems TNM, and possibly incorporating molecular features of gastrointestinal and pancreatic endocrine tumors will provide clinicians with effective means of classification and prognostication of patients with these tumors.     

Antiandrogen ICI 176,334 does not prevent development of androgen insensitivity in S115 mouse mammary tumour cells

Many forms of endocrine therapy for steroid-sensitive tumours involve regimes of steroid agonist deprivation by administration of steroid antagonists. The partial or short-lived response to such therapy results from the inevitable progression of the tumour cells to a state of steroid insensitivity. Several cell culture systems have shown that steroid ablation results in loss of steroid sensitivity and we have used an in vitro model here to study the influence of steroid antagonists on this progression. Growth of androgen-responsive S115 mouse mammary tumour cells in the long-term absence of steroid results in a loss of androgen-sensitivity. We have studied here the effects of the pure antiandrogen ICI 176,334 on the growth of S115 cells and on their progression to steroid autonomy. Although a pure antiandrogen in its action on these cells with very low toxicity, it had no protective effect against loss of cellular or molecular androgen-responsive parameters. The clinical implications for endocrine therapy are discussed.     

Pancreatic endocrine tumors - management guidelines (recommended by the Polish Network of Neuroendocrine Tumors)

Pancreatic endocrine tumors (PETs) are rare neoplasms of this organ. The majority of PETs are tumors without hormonal activity. In this publication, we present the diagnostic and therapeutic guidelines for the management of these tumors proposed by the Polish Network of Neuroendocrine Tumors. These guidelines refer to biochemical and location diagnostics, including scintygraphy of somatostatin receptors, endoscopic ultrasonography and other anatomical and functional imaging methods. High importance is attached to correct histopathological diagnosis which determines further management of patients with PETs. Antitumor therapy requires multidirectional procedure, and therefore the rules of surgical treatment, biotherapy, chemotherapy and peptide receptor radionuclide therapy are discussed.     

The present status of the adjuvant endocrine treatment

Adjuvant therapy of breast cancer is accepted as a useful method for reducing mortality in patients with histologically axillary involved lymph nodes. Polychemotherapy regimens and hormonal treatment procedures are used to reach this goal. Hormonal treatment seems to be useful especially in selected patients. This article deals with (a) new methods for selecting hormone-responsive tumors and patients, and (b) it will give a brief overview of major publications concerning adjuvant endocrine therapy and (c) will summarize the data from the Gynecological Adjuvant Breast Group (GABG) trials.     

Clinical and biomarker endpoint analysis in neoadjuvant endocrine therapy trials

Neoadjuvant endocrine therapy trials for breast cancer are now a widely accepted investigational approach for oncology cooperative group and pharmaceutical company research programs. However, there remains considerable uncertainty regarding the most suitable endpoints for these studies, in part, because short-term clinical, radiological or biomarker responses have not been fully validated as surrogate endpoints that closely relate to long-term breast cancer outcome. This shortcoming must be addressed before neoadjuvant endocrine treatment can be used as a triage strategy designed to identify patients with endocrine therapy “curable” disease. In this summary, information from published studies is used as a basis to critique clinical trial designs and to suggest experimental endpoints for future validation studies. Three aspects of neoadjuvant endocrine therapy designs are considered: the determination of response; the assessment of surgical outcomes; and biomarker endpoint analysis. Data from the letrozole 024 (LET 024) trial that compared letrozole and tamoxifen is used to illustrate a combined endpoint analysis that integrates both clinical and biomarker information. In addition, the concept of a “cell cycle response” is explored as a simple post-treatment endpoint based on Ki67 analysis that might have properties similar to the pathological complete response endpoint used in neoadjuvant chemotherapy trials.     

Cancer molecular epidemiology: new horizons of prophylaxis

Perspectives of malignant neoplasm prophylaxis based on molecular biology achievements are discussed. Gene variants critical to development of hereditary cancer syndromes, genes modulating malignant neoplasm development risk without hereditary cancer syndrome development, and genes determining tendency of individuals for different malignant neoplasm progress risk increasing lifestyle factors are examined. Molecular epidemiology by using large scale population analysis of cancerogenesis linked genetic polymorphisms prevalence allows determination of risk groups at the most earlier stages of cell transformation or even before the onset of cell malignization and development of goal-based prophylaxis measures based on polymorphism and corresponding cancer type. Epidemiologic analysis of this type allows for earlier diagnostics in risk groups, therapy efficacy increase, disability decrease. Specific therapy on molecular level may be possible in the future.     

Principles of laboratory isolation and identification of the human immunodeficiency virus (HIV)

Diagnosis of human immunodeficiency virus (HIV) infections has relied most frequently on detecting the presence of HIV antibodies in sera. In many situations, however, patients management can be significantly improved if the presence of HIV can be demonstrated in patients' specimens. In this review, the need and value of HIV isolation for confirming the diagnosis of HIV, for disease staging, and for monitoring the effectiveness of antiviral therapy are discussed. The steps involved in isolation of HIV, the cell systems permissive to HIV growth, and the procedures for virus identification are reviewed. Furthermore, methods available for the direct detection of HIV in patients' specimens are summarized. Although isolation of HIV is presently an elaborate procedure, as easier methods become available, it will play a large role in the management of HIV-infected individuals.     

Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy

These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi.     

生长抑素受体介导的放射性核素治疗

生长抑素受体介导的放射性核素治疗(peptide receptor radionuclide therapy,PRRT)是用于不能手术治疗或有远处转移的胃、肠和胰腺等神经内分泌肿瘤病人的一种新型治疗方法,本文旨在综述近年来不同核素标记生长抑素类似物的临床评价及相关研究。     

Molecular pathology in the diagnosis and treatment of non-Hodgkin's lymphomas

The non-Hodgkin's lymphomas encompass a wide spectrum of hematologic neoplasms that exhibit different clinical and biological features. Lymphomas classically have been initially assessed based on their cytologic and histologic features. Morphology alone is often inadequate as similar appearing neoplasms may be immunophenotypically and molecularly heterogeneous. Molecular diagnostic methods can provide an additional level of testing that not only helps refine diagnoses but can provide prognostic information. New methods are being refined that may provide information to establish precise diagnostic profiles, provide targets for therapy and provide more sensitive methods for monitoring the success of treatment. Molecular methods will be increasingly utilized and eventually required as the accepted method of diagnosis and for monitoring the disease. Understanding of the molecular abnormality and the pathogenesis of the neoplasm hopefully will lead to therapeutic intervention aimed at the specific molecular defect or its product. The molecular pathology of the non-Hodgkin's lymphomas is discussed.     

Silver stains in the study of endocrine cells of the gut and pancreas

The usefulness of argentaffin (Masson) and argyrophil (Davenport, Sevier-Munger and Grimelius) staining methods for identification of endocrine cell types in the gastrointestinal tract and pancreas is discussed and comments are made on the techniques themselves. The applicability of silver impregnation methods in the histopathological investigations of endocrine tumours in the above-mentioned organs is outlined, and the chemical background of the silver reactions is briefly reviewed.     

An automatic EEG-based sleep staging system with introducing NAoSP and NAoGP as new metrics for sleep staging systems

Different biological signals are recorded in sleep labs during sleep for the diagnosis and treatment of human sleep problems. Classification of sleep stages with electroencephalography (EEG) is preferred to other biological signals due to its advantages such as providing clinical information, cost-effectiveness, comfort, and ease of use. The evaluation of EEG signals taken during sleep by clinicians is a tiring, time-consuming, and error-prone method. Therefore, it is clinically mandatory to determine sleep stages by using software-supported systems. Like all classification problems, the accuracy rate is used to compare the performance of studies in this domain, but this metric can be accurate when the number of observations is equal in classes. However, since there is not an equal number of observations in sleep stages, this metric is insufficient in the evaluation of such systems. For this purpose, in recent years, Cohen’s kappa coefficient and even the sensitivity of NREM1 have been used for comparing the performance of these systems. Still, none of them examine the system from all dimensions. Therefore, in this study, two new metrics based on the polygon area metric, called the normalized area of sensitivity polygon and normalized area of the general polygon, are proposed for the performance evaluation of sleep staging systems. In addition, a new sleep staging system is introduced using the applications offered by the MATLAB program. The existing systems discussed in the literature were examined with the proposed metrics, and the best systems were compared with the proposed sleep staging system. According to the results, the proposed system excels in comparison with the most advanced machine learning methods. The single-channel method introduced based on the proposed metrics can be used for robust and reliable sleep stage classification from all dimensions required for real-time applications.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09641-2) contains supplementary material, which is available to authorized users.     

Carcinoma of Lung with Adrenal Hyperfunction and Hypercalcemia Treated by Parathyroidectomy

A case of severe hypercalcemia secondary to carcinoma of the lung is described in which hypokalemic alkalosis, renal failure and pancreatitis were also present. The relative importance of the few bone metastases found at autopsy is considered, and a probable endocrine-like effect of the tumour in the development of the hypercalcemia is postulated. Treatment of the hypercalcemia included administration of corticosteroids and disodium EDTA, peritoneal dialysis and subtotal parathyroidectomy; the most effective of these was peritoneal dialysis. Subtotal parathyroidectomy failed to produce a further decrease in serum calcium values. The occurrence of hypokalemic alkalosis in the presence of increased adrenocortical function and its relationship to the carcinoma of the lung are discussed. The possibility that this neoplasm produced two factors which caused systemic effects ordinarily associated with the function of endocrine glands must be considered.     

Neurotoxic states and their investigation--possibility for early detection of poisoning

A highly important function of the nervous system (NS) is to process the information arriving to us from external, environmental sources. This capacity may be discontinued by chemicals restricting the plasticity of the NS, disturbing its adaptability to the ever changing environment. NS and endocrine system are profoundly bound together, changes, disruption of the different regulatory endocrine levels by toxicants may take part in the development of manyfold neural disfunction. The various endocrine levels (integrative, modulatory, regulatory, effector, target gland, etc.) affecting neurotoxicity and affected by neurotoxicity are discussed. The NS is protected against some toxic insults but is rather sensitive to other ones. By electrophysiological and psychophysiological methods, used as sensitive biomarkers the signs of functional disturbances of the NS can be proved both in human investigations and in animal experiments at an early stage of low concentration intoxications when clinical or general laboratory symptoms do not indicate yet the moderate poisoning.     

Thyroid hormones promote endocrine differentiation at expenses of exocrine tissue

Diabetes is caused by loss or dysfunction of pancreatic beta cells. Generation of beta cells in vitro is a promising strategy to develop a full-scale cell therapy against diabetes, and the development of methods without gene transfer may provide safer protocols for human therapy. Here we show that thyroid hormone receptors are expressed in embryonic murine pancreas. Addition of the thyroid hormone T3 in an ex vivo culture model of embryonic (E12.5) dorsal pancreas, mimicking embryonic pancreatic development, promoted an increase of ductal cell number at expenses of the acinar compartment. Double labeled cells expressing specific markers for ductal and acinar cells were observed, suggesting cell reprogramming. Increased mRNA levels of the pro-endocrine gene Ngn3 and an increased number of beta cells were detected in cultures treated previously with T3 suggesting that ductal cells promoted by T3 can subsequently differentiate into endocrine cells. So, indirectly, T3 induced endocrine differentiation. Moreover, T3 induced the expression of the pro-endocrine gene Ngn3 in the acinar 266-6 cell line. The pro-endocrine effect of T3 in the pancreatic explants and in the acinar cell line, was abrogated by the Akt inhibitor Ly294002 indicating the involvement of Akt signaling in this process. Altogether we show numerous evidences that define T3 as a promising candidate to generate endocrine cells from exocrine tissue, using ectopically gene expression free protocols, for cell therapy against diabetes.     

Summary of aromatase inhibitor trials: the past and future

Antagonizing estrogen by inhibition of aromatase has become a mainstay of adjuvant endocrine therapy in women with hormone receptor positive (ER+) breast cancer. Recent trials have shown an incremental gain for the AIs over tamoxifen when given as an up-front alternative to tamoxifen, but additionally added benefit is achieved by giving them in sequence with tamoxifen after either an early switch (2–3 years) or as a late switch (5 years). The true clinical implications of accelerated bone resorption from AIs is becoming better understood and its management defined. AI minimally effect quality of life. The chronic relapsing nature of ER+ breast cancer implies long term therapy will be of benefit in selected patients. Outstanding issues under investigation include optimal duration of endocrine therapy, optimal sequence, optimal agents and whether combining anti-estrogens will yield advantage. The role of AIs is also under investigation in premenopausal women in combination with ovarian function suppression. Identifying prognostic and predictive factors of endocrine therapy is important as is the identification and overcoming of resistance mechanisms. Both tumor and host signatures are being pursued to this end. Optimizing, expanding and extending endocrine therapy is likely to add further to patient outcome.     

Biological and enzymatic treatment of bisphenol A and other endocrine disrupting compounds: a review

Bisphenol A is predominantly used as an intermediate in the production of polycarbonate plastics and epoxy resins. Traces of bisphenol A released into the environment can reach into the wastewater and soil via application of sewage sludge from wastewater treatment systems that receive water containing bisphenol A, or from leachate from uncontrolled landfills. In this study we have made an effort to review the work on the presence of bisphenol A and other related endocrine disrupting compounds in the environment and their impact on the life of living organisms including human beings. Bisphenol A has several implications on the health of human beings as well it can also affect the growth of plants and animals. Number of physicochemical methods such as adsorption, membrane based filtration, ozonation, fenton, electrochemical and photochemical degradation has been used for the removal of bisphenol A. However, these methods have some inherent limitations and therefore cannot be used for large scale treatment of such pollutants. The alternative procedures have attracted the attention of environmental scientists. Biological methods are looking quite promising and these procedures are helpful in the complete degradation of bisphenol A and related compounds. Several bacterial, fungal, and algal strains and mixed cultures have successfully been employed for the degradation of bisphenol A. Recently, enzymatic methods have attracted the attention of the environmentalists for the treatment of bisphenol A and other endocrine disrupting compounds. Numerous types of oxidoreductases; laccases, tyrosinases, manganese peroxidase, lignin peroxidase, polyphenol oxidases, horseradish peroxidase and bitter gourd peroxidase have exhibited their potential for the remediation of such types of compounds. The cytochrome P 450 monooxygenases and hemoglobin have also participated in the degradation of bisphenol A and other related endocrine disrupting compounds. Various redox mediators, surfactants and additives have also enhanced enzymatic oxidation of bisphenol A and other related endocrine disrupting compounds.     

Novel approaches for COVID-19 diagnosis and treatment: a nonsystematic review

Since COVID-19 pandemic has been continuously rising and spreading, several original contributions and review articles on COVID-19 started to appear in the literature. The review articles are mainly focus on the current status of the pandemic along with current status of the corona diagnosis and treatment process. Due to some disadvantages of the currently used methods, the improvement on the novel promising diagnosis and treatment methods of corona virus is very important issue. In this review, after briefly discussing the status of current diagnosis and treatment methods, we present to the scientific community, novel promising methods in the diagnosis and treatment of COVID-19. As with other novel approaches, first, the diagnosis potential of mass spectroscopy and optical spectroscopic methods such as UV/visible, infrared, and Raman spectroscopy coupled with chemometrics will be discussed for the corona virus infected samples based on the relevant literature. In vibrational spectroscopy studies, due to complexity of the data, multivariate analysis methods are also applied to data. The application of multivariate analysis tools that can be used to extract useful information from the data for diagnostic and characterisation purposes is also included in this review. The reviewed methods include hierarchical cluster analysis, principal component analysis, linear and quadratic discriminant analysis, support vector machine algorithm, and one form of neural networks namely deep learning method. Second, novel treatment methods such as photodynamic therapy and the use of nanoparticles in the in-corona virus therapy will be discussed. Finally, the advantages of novel promising diagnosis and treatment methods in COVID-19, over standard methods will be discussed. One of the main aims of this paper is to encourage the scientific community to explore the potential of this novel tools for their use in corona virus characterization, diagnosis, and treatment.