ABSTRACT
Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. GLUT1, FABPpm, MCT4 and SNAT1 genes were significantly overexpressed in carcinomas compared with controls, while expression of CD36/SR-B2, FATP1, FABP4, GLUT4, ASCT2 and LPL was decreased. No differences were found in FATP4, LAT1, MCT1 and FASN. The transcript content of mitochondrial genes such as PGC-1α, TFAM and COX4/1 was similar between groups, while the ß-HAD level declined in ovarian cancer. Additionally, the MCT4 level was reduced and PGC-1α was elevated in cancer tissue from patients with 'small' primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher FABP4 and LPL and lower TFAM expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth.
Subject(s)
Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Female , Gene Expression , Humans , Membrane Transport Proteins/genetics , Ovarian Neoplasms/pathologyABSTRACT
Endometrial cancer (EC) is one of the most frequent female malignancies. Because of a characteristic symptom, vaginal bleeding, EC is often diagnosed in an early stage. Despite that, some EC cases present an atypical course with rapid progression and poor prognosis. There have been multiple studies conducted on molecular profiling of EC in order to improve diagnostics and introduce personalized treatment. Chemokines-a protein family that contributes to inflammatory processes that may promote carcinogenesis-constitute an area of interest. Some chemokines and their receptors present alterations in expression in tumor microenvironment. CXCL12, which binds the receptors CXCR4 and CXCR7, is known for its impact on neoplastic cell proliferation, neovascularization and promotion of epidermal-mesenchymal transition. The CCL2-CCR2 axis additionally plays a pivotal role in EC with mutations in the LKB1 gene and activates tumor-associated macrophages. CCL20 and CCR6 are influenced by the RANK/RANKL pathway and alter the function of lymphocytes and dendritic cells. Another axis, CXCL10-CXCR3, affects the function of NK-cells and, interestingly, presents different roles in various types of tumors. This review article consists of analysis of studies that included the roles of the aforementioned chemokines in EC pathogenesis. Alterations in chemokine expression are described, and possible applications of drugs targeting chemokines are reviewed.
Subject(s)
Chemokines , Endometrial Neoplasms , Chemokines/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Humans , Neovascularization, Pathologic , Tumor Microenvironment/geneticsABSTRACT
Ovarian cancer is the seventh most common cancer in women. It is characterized by a high mortality rate because of its aggressiveness and advanced stage at the time of diagnosis. It is a nonhomogenous group of neoplasms and, of which the molecular basics are still being investigated. Nowadays, the golden standard in the treatment is debulking cytoreductive surgery combined with platinum-based chemotherapy. We have presented the interactions and the resulting perspectives between fatty acid transporters, glucose transporters and ovarian cancer cells. Studies have shown the association between a lipid-rich environment and cancer progression, which suggests the use of correspondent transporter inhibitors as promising chemotherapeutic agents. This review summarizes preclinical and clinical studies highlighting the role of fatty acid transport proteins and glucose transporters in development, growth, metastasizing and its potential use in targeted therapies of ovarian cancer.
Subject(s)
Fatty Acid Transport Proteins/metabolism , Glucose Transport Proteins, Facilitative/metabolism , Obesity/metabolism , Ovarian Neoplasms/metabolism , Animals , Antineoplastic Agents/pharmacology , Female , Humans , Obesity/drug therapy , Ovarian Neoplasms/drug therapyABSTRACT
INTRODUCTION: Enhanced Recovery After Surgery (ERAS) programs have been shown to improve clinical outcomes in gynecologic oncology, with the majority of published reports originating from a small number of specialized centers. It is unclear to what degree ERAS is implemented in hospitals globally. This international survey investigated the status of ERAS protocol implementation in open gynecologic oncology surgery to provide a worldwide perspective on peri-operative practice patterns. METHODS: Requests to participate in an online survey of ERAS practices were distributed via social media (WhatsApp, Twitter, and Social Link). The survey was active between January 15 and March 15, 2020. Additionally, four national gynecologic oncology societies agreed to distribute the study among their members. Respondents were requested to answer a 17-item questionnaire about their ERAS practice preferences in the pre-, intra-, and post-operative periods. RESULTS: Data from 454 respondents representing 62 countries were analyzed. Overall, 37% reported that ERAS was implemented at their institution. The regional distribution was: Europe 38%, Americas 33%, Asia 19%, and Africa 10%. ERAS gynecologic oncology guidelines were well adhered to (>80%) in the domains of deep vein thrombosis prophylaxis, early removal of urinary catheter after surgery, and early introduction of ambulation. Areas with poor adherence to the guidelines included the use of bowel preparation, adoption of modern fasting guidelines, carbohydrate loading, use of nasogastric tubes and peritoneal drains, intra-operative temperature monitoring, and early feeding. CONCLUSION: This international survey of ERAS in open gynecologic oncology surgery shows that, while some practices are consistent with guideline recommendations, many practices contradict the established evidence. Efforts are required to decrease the variation in peri-operative care that exists in order to improve clinical outcomes for patients with gynecologic cancer globally.
Subject(s)
Enhanced Recovery After Surgery , Genital Neoplasms, Female/surgery , Guideline Adherence , Gynecologic Surgical Procedures/methods , Perioperative Care/methods , Attitude of Health Personnel , Female , Humans , Prospective Studies , Surveys and QuestionnairesABSTRACT
BACKGROUND: Burnout syndrome is a serious manifestation of distress among health-care professionals. OBJECTIVE: Due to the specific nature of work in operating theaters, factors that affect the staff performance and therefore predispose to burnout syndrome were assessed. METHODS: Based on the original questionnaire, 254 respondents working in the operating theaters of the university hospital, appraised levels of work satisfaction, sources of stress, and psychosocial burden. Work-related mental stress was assessed using the Meister's questionnaire. Burnout levels were evaluated in the group extended to 316 employees with Maslach Burnout Inventory. RESULTS: Work satisfaction analysis indicated unsatisfactory management and remuneration as the negative agents. The majority of the respondents emphasized the maintenance of medical records as a prominent stress factor. A large number of participants (n = 221; 87%) described work as emotionally burdensome. The results showed that the highest burden was related to the following variables: time pressure, responsibility, problems, and conflicts. The examined group was qualified to the second degree of mental load related to the work. Similarly, the entire group reached a high level of emotional exhaustion. CONCLUSIONS: Presented data indicate the need of evaluation to minimize occupational burnout problem.
ABSTRACT
BACKGROUND: Two concurrent malignancies present in a young person is an extremely rare condition. Diagnoses of gastric cancer primarily concern older patients. There are very few reports of concomitant Krukenberg tumor and germ-cell ovarian malignancy. CASE: A 19-year-old girl was admitted to the gynecologic oncology department with symptoms of advanced malignancy. Radiological imaging revealed disseminated neoplastic disease with bulky adnexal tumors. Cytoreductive surgery was performed, achieving no visible disease (Tâ¯=â¯0 cm). The final pathology report confirmed metastatic mixed adenoneuroendocrine carcinoma (MANEC) in both ovaries, originating from the gastrointestinal tract. Moreover, the primary germ cell yolk sac tumor was found in the left ovary. CONCLUSION: In cases of concomitant gastric and ovarian tumors, metastatic disease (Krukenberg tumor) should be considered in the differential diagnosis. This concerns even adolescent patients. In particular cases, including tumors with germ cell components, primary debulking surgery is crucial for prognosis.
Subject(s)
Adenocarcinoma/pathology , Endodermal Sinus Tumor/pathology , Neoplasms, Germ Cell and Embryonal/pathology , Ovarian Neoplasms/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Diagnosis, Differential , Endodermal Sinus Tumor/diagnosis , Endodermal Sinus Tumor/surgery , Female , Humans , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/surgery , Neoplasms, Multiple Primary , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Stomach Neoplasms/diagnosis , Stomach Neoplasms/secondary , Stomach Neoplasms/surgery , Young AdultABSTRACT
Due to improved efficacy of antitumour treatment in the general population, there are increasingly more childhood cancer survivors. However, some of these survivors are at risk of distant complications including cardiovascular disease. We aimed to examine the risk of overweight/obesity and abnormal body composition in a large group of patients from our paediatric oncology centre. We used anthropometric methods and electrical bioimpedance to assess these features, and then determined their association with disease and treatment. We found patients treated for leukaemia/lymphoma (especially boys) had significantly higher rates of overweight/obesity compared to the other patient groups. On the contrary, overweight/obesity was more common in girls among patients treated for solid tumours. Patients treated for leukaemia/lymphoma were characterised by a higher body fat content compared to those treated for solid tumours and controls. During treatment for cancer, patients had a higher percentage of muscle mass deficiency compared to those in the control group. Our regression analysis showed time from completion of treatment, gender and type of therapy (radiotherapy, megachemotherapy) were associated with body weight and body composition including fat and muscle content. We recommend paediatricians and general practitioners should actively try to detect and prevent cardiovascular disease among childhood cancer survivors.
ABSTRACT
Overweight, obesity, and metabolic syndrome in paediatrics represent issues of increasing importance. To complete diagnostics and extend patient monitoring, body composition measurements can be used. Nowadays there are a number of methods that allow the esti-mation of the content of individual tissues. Their accuracy and replicability, contributing to the measurement's credibility, are the subject of numerous scientific publications. While choosing a method, one has to know its basic assumptions and be aware of the assets and weaknesses, as well as its cost. The mentioned aspects will be discussed in this article. Reference methods considered as most precise are multicomponent models (3C, 4C), requiring several (usually three) measurements with the use of various devices, which improves the precision of calculating the fraction of a given body composition component (fat, water, minerals, and/or protein). Therefore, the need to estimate tissue content with mathematical models can be minimised. The choice of the methods forming a multicomponent model differs depending on the place of the examination. However, the 3C and 4C models are time-consuming and require sustained coopera-tion with young patients. Moreover, measurements can only be taken by trained staff that use expensive, specialised equipment. The examination cost can be reduced by the use of screening methods, such as anthropometrics and more advanced bioelectrical impedance analysis (BIA). Due to published comparisons with reference methods, the precision limits of screening methods are known. However, when executed correctly, measurements obtained with these methods have an acceptable replicability and can become a valuable tool in everyday practice.
Subject(s)
Body Composition , Overweight/metabolism , Anthropometry , Body Mass Index , Child , Electric Impedance , Humans , Overweight/diagnosis , Overweight/physiopathology , Pediatrics/methodsABSTRACT
With the increasing recognition of overweight, obesity, and metabolic diseases in paediatrics, there is a need to apply more precise diag-nostic methods to individualise the procedures and improve their monitoring. Advanced methods of evaluating body composition are a valuable addition to body weighing because they provide more precise data than screening methods such as anthropometry and bioe-lectrical impedance analysis (BIA). However, they require expensive equipment and highly trained staff. The availability of methods used in paediatrics is increasing. The article discusses the technical assumptions and summarises data from literature concerning the accuracy of chosen methods. From those, dual-energy X-ray absorptiometry (DXA) is distinguished as being widely accepted. Not only does it serve to evaluate bone density, but also to assess fat mass, making it a crucial element of multicomponent models (3C, 4C), which is often used separately as a reference method for other techniques. Methods based on body volume measurement are also of great importance. Traditionally they include hydrodensitometry (HW), which is being displaced by air displacement plethysmography (ADP), which is more acceptable among young patients. Numerous publications indicate that ADP may become a valuable alternative for widely used DXA. Isotope dilution methods are less popular in paediatrics, due to their cost and limited credibility, but are more commonly used among adults. The last group comprises imaging methods rarely used in the discussed indication. With the knowledge of available techniques and current clinical situation one can, for the patient's benefit, decide between screening and advanced techniques of body composition measurement.