Uca1 in cisplatin induced ovarian cancer cell resistance

Further mechanistic studies revealed that UCA1 could sponge endogenous miRp and inhibit its activity. Colorectal cancer CRC is the third most prevalent cancer type and the third leading cause of cancer-related deaths worldwide 1. The occurrence and progression of CRC is a multi-step process involving in the deregulation of multiple oncogenes and tumor suppressors 2.

Uca1 in cisplatin induced ovarian cancer cell resistance

Uca1 in cisplatin induced ovarian cancer cell resistance

The vast majority of ovarian cancer patients diagnosed with an advanced-stage disease undergo debulking surgery followed by adjuvant chemotherapy consisting of a platinum agent typically carboplatin alone or in combination with a taxane paclitaxel [ 2 ].

Initially, seventy percent of the women respond to this therapy, but unfortunately the majority of these patients eventually relapse due to drug-resistant recurrent disease and die due to peritoneal metastasis [ 3 ].

Cancer Chemotherapy and Pharmacology Page 14

The presence of ascites is associated with a poor prognosis [ 49 ]. Microscopic inspection of ascites display a complex heterogeneous picture of cellular environment constituting single cells, floating multicellular aggregates of non-adherent cells, cancer-associated fibroblasts, myeloid cells, activated mesothelial cells and cancer stem cells CSCs [ 10—12 ].

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Extensive seeding of these floating cells on the uterus, sigmoid colon and omentum is frequently encountered in advanced-stage and recurrent patients and ultimately leads to disruption of major organs and eventually death [ 7 ]. During the course of recurrence, cells within the small microscopic residual cellular aggregates release soluble pro-angiogenic mediators, which diffuse out from the tumor population and bind to endothelial cells of mature blood vessels leading to angiogenesis, which sets the tumor expansion and recurrence in motion [ 13 ].

Hence, the presence of floating cellular aggregates, commonly known as spheroids, in the ascites of ovarian cancer patients is strongly associated with recurrence, and there is an urgent need to study these spheroids in the ascites in order to establish the mechanisms of recurrence.

Mechanisms underlying the development of resistance to platinum-based agents have been well characterized in other cancers and include DNA repair mechanisms, altered cellular transport of the drugs, increased antioxidant production, and reduction of apoptosis [ 14—16 ]. Elevated gene expression affecting cellular transport, DNA repair, apoptosis, cell-extracellular matrix and cell-cell adhesion has been observed in ovarian cancer patient's samples resistant to platinum-based therapy [ 17—19 ].

Uca1 in cisplatin induced ovarian cancer cell resistance

Taxanes were originally used as an alternative to platinum based agents in order to overcome platinum resistance in patients [ 20 ]. The development of taxane resistance has also been well studied and characterized [ 21, 22 ]. Typical mechanisms of paclitaxel resistance involve alteration in drug transport, altered expression of microtubule proteins, expression of taxane metabolizing proteins and altered cell signaling resulting in reduced apoptosis [ 22—25 ].

The roles of some of these factors in cancer patients in response to taxane treatment e. In recent studies, we have demonstrated ovarian CSCs to be involved with resistance to both platinum and taxane-based chemotherapies [ 26, 27 ].

We and others have also shown recurrent ovarian tumors to be enriched with CSCs and mediators of pathways that regulate CSCs, suggesting that CSCs may contribute to the development of recurrence [ 10, 11 28, 29 ].

To date most of the research conducted to understand the chemoresistance mechanisms have used cancer cell lines and few data are available on the relevance of these studies on the potential mechanisms of chemoresistance in clinical samples [ 30, 31 ].

These studies, although important, used tumor sections, which are likely to present a complex molecular profile of not only chemoresistant tumor cells but also associated stroma and infiltrated cells.

As a consequence, these mixed genetic profiles may not truly represent the associated pathways regulating chemoresistance in tumor cells; hence, such results may misrepresent the targets proposed for future therapeutic interventions.

Isolated tumor cells that survive chemotherapy treatments in patients are likely to experience changes in gene expression allowing them to withstand the selective pressure of the drugs. These phenotypically changed tumor cells are likely to exhibit a molecular signature associated with chemoresistance when compared to the gene expression profile of isolated tumor cells before chemotherapy treatment.

In the present study, we have used our recently described novel separation technique to isolate tumor cells from the ascites of advanced-stage CN and CR serous ovarian cancer patients [ 10 ].

Ascites samples were collected from patients not matched at the time of surgery prior to chemotherapy treatment CN and at different time points during recurrence CR.

Our data identified novel genes and associated pathways which may have clinical relevance in designing therapeutic interventions for ovarian cancer patients. To our knowledge this is the first study, which has demonstrated a distinct molecular profile of isolated tumor cells from the ascites of CR patients.

The histopathological diagnosis, tumor grades and stages were determined by independent staff pathologists as part of the clinical diagnosis.

Apart from As22 which was collected twice from the same patient As22C and D during sequential ascites removal within a month, other samples were from individual cases. These patients had partial response to the first and subsequent lines of chemotherapy.

The chemotherapy agents administered to patients, and the number of chemotherapy cycles varied from patient to patient and are indicated in Table 1. In CR group, ascites was collected from patients at recurrence after the patients have received the cycles of chemotherapy described in Table 1.Google - Adrenal Cancer (7 unread) Google - Adrenocortical Carcinoma (6 unread) PubMed - Adrenal Cancer ( unread) PubMed - Adrenocortical Carcinoma (64 unread) Trial - Adrenal Cancer (39 unread) Trial - Adrenocortical Carcinoma (13 unread).

The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma. March 01, A 60 kDa prolactin variant secreted by cervical cancer cells modulates apoptosis and cytokine production. Shi L, Chen ZG, Wu LL, et al ().

miR reverses cisplatin resistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway. Asian Pac J Cancer Prev, 15, Objective: The therapeutic potential of cisplatin in ovarian cancer treatment is limited by the occurrence of cellular resistance.

To explore the role of long non-coding RNA UCA1 in cisplatin induced ovarian cancer cell resistance.

Methods: Twenty-four ovarian cancer tissues and sixteen normal tissues were used to assess the expression of UCA1 RNA.

After expression UCA1 in SKOV3 cells, the cell migration, . Resistence of ovarian cancer cells to paclitaxel and cisplatin is associated with a reduced expression of miRc, miR, and miR, which results in activation of M-CSF, the known factor of resistance . Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer ().Tobacco smoking, alcohol consumption and human papilloma virus (HPV) infections have been associated with the occurrence of HNSCC.

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