Circulating Tumor Cells Case Study

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

Some have argued that important information related to the way in which, and the rapidity in which, cancer cells metastases has been obtained by this study. But this has been highly debated (Standler, 1997).

∆CT Comparison between Asthmatic (A) and Non-Asthmatic (N) Epithelial Cells. Gene expression as normalized to β-actin, a housekeeping gene, in media (baseline expression). N epithelial cells are from a non-asthmatic donor, and A epithelial cells are from an asthmatic donor. CT is the threshold concentration at which PCR product is detectable. ∆CT = CTgene of interest – CThousekeeping gene (ß-actin). (Higher ∆CT reflects log2 lower concentrations.)

Angiogenesis must be present for this occur, allowing cancer to spread to the blood, "thus the higher the density of new blood vessels within some tumors, the higher is the risk of metastasis of that tumor" (Mandal, 2014). Tumors have been documented to grow and spread without a direct blood supply and due to this physicians' are trying to discover ways to block tumor angiogenesis by investigating natural and synthetic inhibitors called "antiangiogenic agents" (National Cancer Institute, 2011). The goal is to slow the growth of cancer or prevent the disease entirely. According to the National Cancer Institute, "when vascular endothelial growth factor (VEGF) and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels" (2011, p. 1).

Tumor profiling is another form of advancement to help cure breast cancer. Tumor profiling allows researchers to better understand the genes in cancer cells. In this article found on the Susan G. Koman website, the ability to profile thousands of genes found in tumors is helpful in determining how likely breast cancer will reoccur and probable treatment. “The gene profiles of some tumors may help predict whether the cancer is more likely to recur and metastasize. Tumors with gene profiles showing a high risk of breast cancer recurrence or metastasis may be more likely to benefit from chemotherapy than tumors with gene profiles showing a low risk” (Susan G. Koman).

In the journal Science Translational Medicine, investigators from Cold Spring Harbor Laboratory (CSHL) and the Dana-Farber Cancer Institute, explain how they used electron microscopy to observe

1). In microfluidic flows, particles can migrate one place to another place streamlines to focus at specific position in micro channels because of the inertial forces that overused for high throughput, size based particle and separation of cell. In other words, migration of particles occurs because of the inertial lift forces. Existing of inertial microfluidics devices provide to good separation resolution. In contrast, the use of inertial microfluidics is limited by the large red blood cells and diluted blood samples. However, many researchers use high throughput blood separation as dean flow technique with CTCs isolation from blood. In this way, they may solve the dilution problem a little bit. Consequently, although many recent advances in inertial microfluidics, there is a still need new technologies that provide continuous, high throughput and purity of viable CTCs from large blood

Another biomarker that can be observed in response to cancer is ct-DNA. Ct-DNA refers to fragments of DNA from tumors found circulating in the blood stream. A recent study indicated that observing ct-DNA could have multiple useful applications for oncologists. Ct-DNA analysis during treatment could serve as an indication of how tumors react to treatment methods and whether recurrence is likely. Detecting ct-DNA in the bloodstream could even serve as an early sign of cancer, observable before imaging tests even show tumors. However, ct-DNA analysis has not yet proved to be a replacement for LDCT

Cancer cells migrating in the circulation are called circulating tumor cells (CTCs), which are proposed to be a promising target to interrupt distant metastatic cascades [4]. This process is likely common for all metastatic cancer cells regardless of the target organ.

Over 240,000 women will be diagnosed with breast cancer in 2014 and it is estimated that 40,000 will not survive this terrible disease. Although these numbers seem daunting, believe it or not, breast cancer survival rates are actually on the incline. Many researchers and doctors believe this is due to the advances in treatment of cancers and in earlier detection which is the key in fighting almost any cancer; early detection. Women are taught to do monthly self-examinations to detect anything ‘out of the

Cells can enter small blood vessels and get into the bloodstream. Cancer cells that do that are called circulating tumor cells. The circulating blood sweeps up cancer cells as the blood is circulating and carries the cancer cells until they become attached

Microscopically, the tumor cells may grow in nests, sheets, cords or single cell. Glandular formation differes between cases, the cells also show considerable variation, ranging from small cells with relatively uniform nuclei to markedly pleomorphic cells. Mitotic figures are evident and necrosis may occur, myoepithelial cells are absent, based on morphology some other sub-types of IDC are present. (34)

Distant metastases are mostly identified in patients of osteosarcoma with the estimation of about 85% after surgery. Mostly they occur in lungs however it may also metastasizes to soft tissues and other different bone. Osteosarcoma is lethal because of pulmonary metastasis with widespread progression that leads to respiratory failure. Tumor metastasis and invasion are multistep complex process in which tumor cells alter cell–extracellular matrix (ECM) associations at the primary tumor site to invade adjacent tissues and thus translocated through the vascular vessels to other systems to form secondary tumors there. MMPs are family of proteolytic enzyme that plays an essential role in tumor metastasis and invasion by breaking the ECM and basement

Genetic and phenotypic variation is observed between tumors of different tissue and cell types which mainly due to tumor heterogeneity. Heterogeneity is therefore as an important feature of malignant tumor in diverse genetic backgrounds, pathological patterns, differentiation stages, genetic mutation spectrum, transcriptomics and proteomics gene expression profile, et al. It indicates the high complexity and diversity in cancer progression. Tumor heterogeneity and drug resistance are great challenges for precision oncology and are taken account for the process of research and development of new diagnostic methods and further antitumor agents. Tumor heterogeneity is an important prognostic factor which could be manifested with medical imaging.

Tumor angiogenesis refers to an attribute of tumor cells residing with the capacity to elicit continuously the growth of new capillary endothelium. Tumor angiogenesis occurs by recruitment of endothelial cell precursor or by sprouting of existing capillaries as in physiologic angiogenesis. Angiogenesis (the formation of new blood vessels) is implicated in the pathogenesis of many chronic diseases including cancer. Angiogenesis in the tumor mass permits growth and invasiveness of the cancer cells as it is believed to be essential for the delivery of essential nutrients and oxygen to the tumor microenvironment. Clustered evidence suggests that angiogenesis is a critical event in the progression of solid tumors because tumor growth beyond 2 to