Cancer is a leading cause of morbidity and mortality worldwide. Over the past decades, the concept of precision cancer medicine has emerged as a novel approach in the field of oncology that aims to tailor the most effective treatment options to each individual cancer patient based on the genetic profile of the tumor of each individual patient. Recently, tissue biopsy has become an essential part of cancer care and is widely used to characterize the tumor. However, tissue biopsy techniques face different challenges due to their invasiveness, cost, time, and adversity in potential sampling due to tissue heterogeneity. To overcome these issues, a non-invasive approach has developed, which is known as liquid biopsy. It is a simple, fast, and worthwhile technique based on the analysis of circulating tumor DNA (which is a fraction of cfDNA), circulating tumor cells (CTCs), and other tumor-derived material in blood plasma. This review provides an overview of the concept of liquid biopsy and briefly discusses the role of ctDNA and CTC analysis as tools for early diagnosis and prognosis of cancer. In this review, we also speculate on the advantages of liquid biopsy as opposed to tissue biopsy and postulate that liquid biopsy may be a comprehensive approach to overcome the current limitations associated with costly, invasive, and time-consuming tissue biopsy.

To study the various types of neurons in layer IIa in the piriform cortex (PC) and the spatial distribution of their axons, axon collaterals of three neurons in layer IIa were labeled and quantitatively analyzed by intracellular injection of biocytin in the guinea pig. Individual neurons have highly distributed axon collaterals, which display a little tendency toward patchy concentrations inside as well as outside the PC. One semilunar cell in the posterior PC had 54-mm-long axon collaterals and 4,200 boutons, out of which 2,100 (49% of the total number of boutons) were distributed in the PC. One semilunar-pyramidal transitional cell in the posterior PC had 256-mm-long axon collaterals and 23,000 boutons, out of which 16,100 (70% of the total number of boutons) and 4,000 (18% of the total number of boutons) were respectively distributed in all layers and in layer Ia of the PC. One multipolar cell in the posterior PC had 188-mm-long axon collaterals and 18,000 boutons, out of which 13,700 (78% of the total number of boutons) were distributed in the PC. Our results revealed that the connection patterns of individual cells in layer IIa have most of the features required for an associative neural network, which may function as a content-addressable memory for the association of odor stimuli.

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The olfactory bulb of the musk shrew, Suncus murinus, is characterized by the presence of various interneurons. Our previous report (Kakuta et al., 2001) demonstrated that positive immunoreactions for calretinin were observed in periglomerular and perinidal cells in the glomerular layer, small ovoid neurons in the external plexiform layer, and granule cells in the granule cell layer of the olfactory bulb in the musk shrew aged 1 to 5 weeks, in addition to calretinin-immunoreactive bipolar cells distributed in the anterior subependymal layer and in each layer of the olfactory bulb. To examine the origin and migration of interneurons of the olfactory bulb, we labeled generated cells by injecting 28-day-old musk shrews with 5-bromo-2'-deoxyuridine (BrdU), and detected the labeled progeny cells that survived after several intervals. BrdU-labeled cells originated in the subependymal layer around the anterior horn of the lateral ventricle, and rostrally migrated in the subependymal layer from the anterior wall of the lateral ventricle into the center of the olfactory bulb, where they radially migrated into the granule cell layer, external plexiform layer, and glomerular layer. It took 2 days to migrate rostrally in the subependymal layer from the anterior lateral ventricle to the center of the olfactory bulb, and 2 to 6 days to migrate radially from the bulbar subependymal layer into the three layers mentioned. The rate of rostralward migration of the labeled cells was estimated to be 38 microm/h, while that of radial migration, 7 to 25 microm/h. The present BrdU-labeling study, together with our previous immunohistochemical study (Kakuta et al., 2001), indicates that anterior subependymal cells differentiate into granule cells in the granule cell layer, into Van Gehuchten cells in the external plexiform layer, and into periglomerular and perinidal cells in the glomerular layer of the olfactory bulb in the musk shrew.

Genomic instability is considered a fundamental factor involved in any neoplastic disease. Consequently, the genetically unstable cells contribute to intratumoral genetic heterogeneity and phenotypic diversity of cancer. These genetic alterations can be detected by several diagnostic techniques of molecular biology and the detection of alteration in genomic integrity may serve as reliable genetic molecular markers for the early detection of cancer or cancer-related abnormal changes in the body cells. These genetic molecular markers can detect cancer earlier than any other method of cancer diagnosis, once a tumor is diagnosed, then replacement or therapeutic manipulation of these cancer-related abnormal genetic changes can be possible, which leads toward effective and target-specific cancer treatment and in many cases, personalized treatment of cancer could be performed without the adverse effects of chemotherapy and radiotherapy. In this review, we describe how these genetic molecular markers can be detected and the possible ways for the application of this gene diagnosis for gene therapy that can attack cancerous cells, directly or indirectly, which lead to overall improved management and quality of life for a cancer patient.