Mucins in pancreatic cancer: A well‐established but promising family for diagnosis,prognosis and therapy

Mucins are a family of multifunctional glycoproteins that mostly line the surface of epithelial cells in the gastrointestinal tract and exert pivotal roles in gut lubrication and protection. Pancreatic cancer is a lethal disease with poor early diagnosis, limited therapeutic effects, and high numbers of cancer‐related deaths. In this review, we introduce the expression profiles of mucins in the normal pancreas, pancreatic precursor neoplasia and pancreatic cancer. Mucins in the pancreas contribute to biological processes such as the protection, lubrication and moisturization of epithelial tissues. They also participate in the carcinogenesis of pancreatic cancer and are used as diagnostic biomarkers and therapeutic targets. Herein, we discuss the important roles of mucins that lead to the lethality of pancreatic adenocarcinoma, particularly MUC1, MUC4, MUC5AC and MUC16 in disease progression, and present a comprehensive analysis of the clinical application of mucins and their promising roles in cancer treatment to gain a better understanding of the role of mucins in pancreatic cancer.     

Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy

Multiple sclerosis is a chronic inflammatory disease of the nervous system in which a T-cell-mediated inflammatory process is associated with destruction of myelin sheaths. Although demyelination is the primary event, axons are also destroyed in the lesions, and the loss of axons correlates with permanent functional deficit. Here, we discuss evidence that demyelination and axonal destruction follow different pathogenetic pathways in subgroups of patients. This might, at least in part, explain the heterogeneity in genetic susceptibility, clinical presentation and response to treatment observed between individuals.     

Microcalcifications in breast cancer: From pathophysiology to diagnosis and prognosis

The implementation of mammographic screening programmes in many countries has been linked to a marked increase in early detection and improved prognosis for breast cancer patients. Breast tumours can be detected by assessing several features in mammographic images but one of the most common are the presence of small deposits of calcium known as microcalcifications, which in many cases may be the only detectable sign of a breast tumour. In addition to their efficacy in the detection of breast cancer, the presence of microcalcifications within a breast tumour may also convey useful prognostic information. Breast tumours with associated calcifications display an increased rate of HER2 overexpression as well as decreased survival, increased risk of recurrence, high tumour grade and increased likelihood of spread to the lymph nodes. Clearly, the presence of microcalcifications in a tumour is a clinically significant finding, suggesting that a detailed understanding of their formation may improve our knowledge of the early stages of breast tumourigenesis, yet there are no reports which attempt to bring together recent basic science research findings and current knowledge of the clinical significance of microcalcifications. This review will summarise the most current understanding of the formation of calcifications within breast tissue and explore their associated clinical features and prognostic value.     

Immunological approach in the diagnosis, therapy and prognosis of the exocrine pancreatic cancer

The aim of the paper is to outline the most important up-to-date methods regarding the immunological approach in the diagnosis, treatment and prognosis of the exocrine pancreatic cancer, keeping in mind that this localisation of neoplastic disease represents the 5th cause of cancer-related death and especially, an important cause of morbidity. This disease, diagnosed in the past in later stages, being therefore associated with poor results, has turned to be characterized by increasing survival rates due to the improvements in diagnostic and therapeutic methods. Regarding the diagnosis strategy, progress was made in imagistic sphera, aiming: 1. an early diagnosis of pancreatic cancer and, implicitly, a high resectability rate of tumor, and 2. an evaluation of the timing for palliative therapeutic methods. So that, if in the past the diagnostic algorithm meant endoscopic retrograde-cholangio-pancreatography, computed tomography and angiography, at present it means nuclear magnetic resonance and helicoidal tomography. Concerning the treatment, it has to be multidisciplinary (surgery, radiotherapy, chemotherapy, immunotherapy), complex, because, after a resection for cure (R0), the main stay of the treatment, the mean survival at 5 years is 3%-28% and the rate of recurrences is 33%-80%. Biological therapy (sometimes called immunotherapy, biotherapy or biological response modifier therapy) is a relatively new addition to the family of cancer treatments that also includes surgery, chemotherapy and radiation therapy. Biological therapies are designed to repair, stimulate or enhance the immune system responses. We shall try to point out how the exocrine pancreatic cancers, the same stages and undergoing the same approaches, have had different responses due to a different biological behavior and how the biological response modifiers (interferons, interleukins, colony-stimulating factors, monoclonal antibodies and vaccines) can improve the results in pancreatic cancer.     

Tumor-derived extracellular vesicles: Potential tool for cancer diagnosis,prognosis, and therapy

Various types of cancer pose a notable threat to human health globally. To date, many researchers have undertaken the search for anticancer therapies. However, many anticancer therapeutic approaches accompany many undesirable hazards. In this respect, extracellular vesicles as a whole gained excessive attention from the research community owing to their remarkable potential for delivery of anticancer agents since they are involved in distal intercellular communication via biological cargoes. With the discovery of the fact that tumor cells discharge huge quantities of EVs, new insights have been developed in cancer diagnosis and treatment. Tumor-derived extracellular vesicles (TD-EVs) can be distinguished from the normal cell-derived EVs due to the presence of specific labels on their surface. TD-EVs carry specific oncogenic proteins and the nucleic acids on their surface membrane that participate in tumor progression. Moreover, the proportion of these nucleic acids and the protein greatly varies among malignant and healthy cell-derived EVs. The diagnostic potential of TD-EVs can be implied for the more precise and early-stage detection of cancer that was impossible in the past. This review examines the recent progress in prognostic, diagnostic, and therapeutic potential of the EVs derived from the tumor cells.     

MicroRNAs: Potential biomarkers for cancer diagnosis,prognosis and targets for therapy

MicroRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The widespread and comprehensive use of microRNA microarrays has enabled the identification of a number of microRNAs as potential biomarkers for cancer. It is encouraging to report that microRNAs have remarkable stability in both formalin-fixed tissue and blood. Many microRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified microRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many microRNA targets and their relevant pathways has contributed to the development of microRNA-based therapeutics, but the developing progress of antisense or siRNA drugs has been hampered by stability, specificity and delivery problems. This review summarizes the most significant and latest findings of original researches on microRNAs involvement in cancer, focusing on the potential of cancer-related microRNAs as biomarkers for diagnosis, prognosis and targets for therapy.     

High-risk estrogen-receptor-positive breast cancer: identification and implications for therapy

The estrogen receptor (ER) has long been recognized as a key discriminative feature of breast cancer, which carries profound implications for management. However, recent advances in the understanding of breast cancer heterogeneity have demonstrated the importance of biologic context to the interpretation of ER as a prognostic and predictive factor. The use of tumor subtyping methods and prognostic indicators based on molecular profiling of tumor tissue is now helping to delineate high-risk ER-positive cancer types that have distinct risk and treatment response profiles. These new approaches to breast cancer classification will have a major impact on the conduct of clinical trials and individual patient assessment in the future.     

The potential role of miR-29 in health and cancer diagnosis,prognosis, and therapy

miR-29 family is one of the small noncoding RNAs and has a very important role in many physiologic and pathologic functions through regulating the target genes that play roles in various bioprocesses such as proliferation, survival, apoptosis, and angiogenesis. Thus, we aim to survey the potential of the miR-29 family in normal model and development and progression of malignancy in this study. In addition, the potential role of miR-29 family has been studied as the clinical marker for the diagnosis and prognosis of many cancers as the potential targets to treat cancer. Moreover, it was stated in summary that the herbal compounds can regulate miR-29 family in cancers. Therefore, regulating the expression of the miR-29 family in a variety of cancers can be a new strategy to obtain better results from cancerous patients’ treatment in the future.     

Racial disparity in breast cancer: can it be mattered for prognosis and therapy

Breast cancer (BC) has emerged as a deadly disease that affects the lives of millions of women worldwide. It is the second leading cause of cancer-related deaths in the United States. Advancements in BC screening, preventive measures and treatment have resulted in significant decline in BC related deaths. However, unacceptable levels of racial disparity have been consistently reported, especially in African-American (AA) women compared to European American (EA). AA women go through worse prognosis, shorter survival time and higher mortality rates, despite higher cancer incidence reported in EA. These disparities are independent of socioeconomic status, access to healthcare or age, or even the stage of BC. Recent race-specific genetic and epigenetic studies have reported biological causes, which form the crux of this review. However, the developments are just the tip of the iceberg. Prioritizing primary research towards studying race-specific tumor microenvironment and biological composition of the host system in delineating the cause of these disparities is utmost necessary to ameliorate the disparity and design appropriate diagnosis/treatment regimen for AA women suffering from BC. In this review article, we discuss emerging trends and exciting discoveries that reveal how genetic/epigenetic circuitry contributed to racial disparity and discussed the strategies that may help in future therapeutic development.     

雌激素受体信号通路在乳腺癌发生和治疗中的作用

雌激素受体信号通路在调控乳腺细胞增殖和凋亡等生理机能中发挥重要功能,该通路出现调控异常时可导致乳腺癌发生。雌激素受体在乳腺癌发生中的作用机制包括核受体介导的基因组信号通路和膜受体介导的非基因组信号通路以及二者的相互作用。基于雌激素受体信号通路及其关键信号分子的靶向治疗是开展乳腺癌治疗的重要策略与有效途径。对雌激素受体结构以及雌激素受体信号通路在乳腺癌发生和治疗中的作用作一综述。     

Sphingolipids in cancer: regulation of pathogenesis and therapy

Sphingolipids are known to play important roles in the regulation of cell proliferation, response to chemotherapeutic agents, and/or prevention of cancer. Recently, significant progress has been made in the identification of the enzymes and their biochemical functions involved in sphingolipid metabolism. In addition, development of new techniques for the quantitative analysis of sphingolipids at their physiological levels has facilitated studies to examine distinct functions of these bioactive sphingolipids in cancer pathogenesis and therapy. This review will focus on the recent developments regarding the roles of bioactive sphingolipids in the regulation of cell growth/proliferation, and anti-cancer therapeutics.     

循环肿瘤细胞在乳腺癌预后评价中的应用和意义

循环肿瘤细胞(CTCs)是导致肿瘤转移的主要原因,它在外周血中的含量与乳腺癌的转移、治疗和预后有密切的关系.本文对于CTCs的概念、检测方法、以及作为肿瘤转移预测指标的优势进行了综述.并对其在临床上的运用前景进行了展望.     

MiRNAs roles in the diagnosis,prognosis and treatment of colorectal cancer

ABSTRACT

Introduction: The liver is the main location for metastasization in stage IV colorectal cancers.

Areas covered: This review intends to comprehensively present the most important studies conducted in the past few years concerning the role of miRNAs in colorectal cancer liver metastases, trying to clarify some aspects regarding tumor biology and favorite liver metastasization site.

Expert commentary: Recent advances in tissue and serum RNA extraction has considerably improved the field of microRNAs studies. These molecules known to play a crucial role in the metastatic stage indicate a starting point in the development of clinical biomarkers with a possible role in the stratification of high-risk patients for adequate treatment.