This study investigated the role of mitochondrial dynamics and the protein Drp1 in breast cancer cell apoptosis. Previous research showed that breast cancer HTB-22 cells have more fragmented mitochondria compared to non-cancerous controls, indicating a pro-fission phenotype. This study further characterized Drp1 function and found that more Drp1 translocates to the outer mitochondrial membrane in HTB-22 cells, which may explain their fragmented mitochondria. Future work will examine downstream apoptotic proteins like cytochrome c to determine how breast cancer cells resist apoptosis and continue proliferating.
Potential Role of Monocyte Chemotactic Protein 1 (MCP-1) in the Breast Cancer...Marion Hartmann
MCP-1 has a potentially important role in the breast tumour microenvironment.
The results presented suggest it may exert its effect by promotion of tumour cell survival through up-regulation of anti-apoptotic factors and pro-migratory factors and thus may be a target for therapeutic intervention.
Potential Role of Monocyte Chemotactic Protein 1 (MCP-1) in the Breast Cancer...Marion Hartmann
MCP-1 has a potentially important role in the breast tumour microenvironment.
The results presented suggest it may exert its effect by promotion of tumour cell survival through up-regulation of anti-apoptotic factors and pro-migratory factors and thus may be a target for therapeutic intervention.
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
Hallmarks of cancer and radiopharmaceuticalsAlice Viana
In this presentation I review the article Hallmarks of cancer: next generation, from Hanahan and Weinberg, and make a parallel with potential and current targets of radiopharmaceuticals for diagnosis and treatment.
The Effect of Oflactomedin1 and Latrophilin2 in Glioblastoma MetastasisTingtingThompson
This is the final poster I presented at the conclusion of the KEYS 2017 program.
Abstract:
Glioblastoma is a lethal brain cancer that is resistant to many treatments. It is observed that cells with both olfactomedin1 and latrophilin2 proteins have enhanced metastatic abilities– cancer spreading. Using the Duolink kit, the steps are: fix cells to coverslips, apply two sets of primary antibodies, apply probes, then image. The probes attach to primary antibodies and hybridize if they are within a certain distance, a circular bridge forms then is amplified and lit up. Strong signal colorations validate the relationship since the kit only amplifies connections between sets of both proteins in close proximity. Future goals consist of furthering investigation on the details of the relationship and reducing invasion. Slowing down the progression of Glioblastoma through limiting spreading makes less harmful treatment options available.
Slide deck used for video presentation to the OCTS conference. Her2-positive CNS metastases plague refractory breast cancer patients. Here we present our wholly novel approach to cell therapy for the treatment of these patients. #celltherapy #oncology #breastcancer
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
Hallmarks of cancer and radiopharmaceuticalsAlice Viana
In this presentation I review the article Hallmarks of cancer: next generation, from Hanahan and Weinberg, and make a parallel with potential and current targets of radiopharmaceuticals for diagnosis and treatment.
The Effect of Oflactomedin1 and Latrophilin2 in Glioblastoma MetastasisTingtingThompson
This is the final poster I presented at the conclusion of the KEYS 2017 program.
Abstract:
Glioblastoma is a lethal brain cancer that is resistant to many treatments. It is observed that cells with both olfactomedin1 and latrophilin2 proteins have enhanced metastatic abilities– cancer spreading. Using the Duolink kit, the steps are: fix cells to coverslips, apply two sets of primary antibodies, apply probes, then image. The probes attach to primary antibodies and hybridize if they are within a certain distance, a circular bridge forms then is amplified and lit up. Strong signal colorations validate the relationship since the kit only amplifies connections between sets of both proteins in close proximity. Future goals consist of furthering investigation on the details of the relationship and reducing invasion. Slowing down the progression of Glioblastoma through limiting spreading makes less harmful treatment options available.
Slide deck used for video presentation to the OCTS conference. Her2-positive CNS metastases plague refractory breast cancer patients. Here we present our wholly novel approach to cell therapy for the treatment of these patients. #celltherapy #oncology #breastcancer
Java is a general-purpose, object-oriented computer programming language that offers special features that allow programs to take advantage of the power and flexibility of the Internet.
Role of notch signalling in deveopment, cancer development and its detailed cancer cell line study for purpose of detailed targetted molecular therapeutics
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
Mitochondria are double membranous organelle, the inner membrane is more larger than the outer one. For this reason the inner membrane of the mitochondria folds inside forming a special figure called creasteae. The inner mitochondrial membrane (IMM) contains the subunits for oxidative phosphorylation (OXPHOS). And this inner mitochondrial membrane coverd by a second membrane called the outer mitochondrial membrane (OMM). We called mitochondria as a power house of cell not only they generates ATP via oxidative phosphorylation they also take part in various biochemical pathways such as- pyrimidine and purine biosynthesis, heme biosynthesis, the regulation of N2 balance in urea cycle, gluconeogenesis, keton body production and fatty acid degradation and elongation. They also take part in cell signalling via regulating the protein-protein interaction or by regulating the cellular concentration of calcium ion(Ca2+) and reactive oxygen species(ROS).
During various biological diseasesmitochondrial morphology altered, as in the case when there is lack of nutrient in our body mitochondria combine together to share their nutrient and alo their DNA and ETC components to maintain their OXPHOS. But in case of high energy demand of a part of body mitochondria undergo division or called fission because they move rapidly than lager one (Zhao et al., 2013). Fission also occur in mitotic cell to share equal amount of mitochondria to the daughter cells. Many questions arise in mitochondrial dinamics but here I am going to answer a most doubtful question- Is mitochondrial dynamics play any role in tumorigenic process? Is any oncogenic signalling play crucial role in morphological alteration of mitochondria?
paraphrase the review in your own wordsThe tumor suppressor PTEN .pdfarihantgiftgallery
paraphrase the review in your own words?
The tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), is
a lipid phosphatase that converts phosphatidylinositol-3, 4, 5- triphosphate (PIP3) into
phosphatidylinositol (4, 5)- diphosphate (PIP2). PTEN is well-known as the most highly mutated
tumor suppressor gene in the p53-post era [66, 67]. Recently, three papers by Nadav Bar and
Rivka Dikstein, Linhua Liu and colleagues, and Laura Poliseno and colleagues, have
demonstrated that PTEN was a bona fide target of miR-22 in a small cohort of cancer cell lines
that are driven from breast cancer, cervical cancer, prostate cancer, and bronchial epithelial
cancer. These studies contradict a uniform role of miR-22, indicating that under certain
circumstances, miR-22 may function as an oncogene because of its antagonistic effects on tumor
suppressive PTEN signaling [26, 68, 69] (Fig. 3). Using various miRNA target prediction
programs and/or RNAhybrid program for evaluating the minimum free energy hybridization,
these three groups all found that miR-22-PTEN was a high scoring miRNA-target pair. Enforced
or reduced expression of miR-22 in human HEK293T, cervical cancer HeLa and breast cancer
MCF-7 cell lines (Nadav Bar and Rivka Dikstein), anti-benzo[a]pyrene-7, 8-diol-9, 10-epoxide
(anti-BPDE)-induced transformed human bronchial epithelial cancer cell line 16HBE-T (Linhua
Liu and colleagues) and prostate cancer cell line DU145 (Laura Poliseno and colleagues),
revealed that miR-22 negatively regulated PTEN protein expression. Intriguingly, an inverse
correlation between miR-22 and PTEN mRNA expression has been presented by Poliseno et al.,
while Liu et al. found that there was no change of PTEN mRNA expression regardless of miR-
22 levels. A similarly inverse association of miR-22 and J. Xiong PTEN protein levels was
observed in 16HBE-T and its parental normal cell line16HBE (Linhua Liu and colleagues), and
in several prostate cancer cell lines, prostate cell lines and a prostate tumor tissue microarray
(Laura Poliseno and colleagues). Furthermore, the mature levels of miR-22 were significantly
increased in these tumor cells versus their normal counterparts. In line with this result, a direct
correlation between miR-22 expression and phosphorylated AKT or between the expression of
miR- 22 and that of DICER was also identified by Laura Poliseno and colleagues. These three
groups all showed that an intact binding site at the 3’UTR of PTEN mRNA was required for
miR-22 targeting. Functional analyses showed that miR-22 could induce apoptosis, inhibited
colony formation and suppressed motility of bronchial epithelial cancer cells (Linhua Liu and
colleagues), and intrinsically promote prostate cancer cell growth and tumorigenesis in tumor-
bearing nude mice (Laura Poliseno and colleagues). Subsequently, the influence of miR-22 on
the downstream signaling of PTEN was tested. Bar et al. showed that miR-22 could stimulate
AKT activity, and i.
P53 Tumor Suppressor Gene: Understanding P53 Based Dietary Anti Cancer Thera...Sheldon Stein
The P53 tumor suppressor gene which has been dubbed both the “Guardian of the Genome” (Lane 1992) and Science “Molecule of the Year”, is directly involved in the initiation of apoptosis and programmed cell death, to prevent an accumulation of abnormal cells. However apoptosis evasion is a characteristic feature of human cancers that promote tumor formation and progression (1). Presently, P53 is known to play a key role in practically all types of human cancers, and the mutation or loss of P53 gene function, can be identified in more than 50% of all human cancer cases worldwide.
This paper was uploaded on behalf of Professor Serge Jurasunas of Lisbon Portugal, www.sergejurasunas.com
The paper goes on to explain the role of the P53 gene and its relationship to Cancer and Apoptosis. It then elaborates on the importance of dietary agents can have a beneficial impact in cancer treatment, and provides a number of case studies. He addresses the importance of the P53 gene and DNA repair, as well as his use of Molecular Markers testing.
Professor Jurasunas believes:
We urgently need to put into clinical practice what we have discovered and learned. Targeting P53 and other genes remain one of the greatest challenges in the treatment of cancer. We have been working now for over 8 years with molecular markers as a diagnostic, prognosis, and follow up to treatment, selected the appropriate bioactive dietary compounds or anticancer agents, exceeding 1000 cases, blood tests, and successes. This may be an incentive for more doctors to venture into this new direction in order to achieve more beneficial results with their patient treatment, especially in cases where we can verify the ones who would be refractory to chemotherapy and have a poor response. It is always best to first check through patient testing, to determine whether or not chemotherapy would be beneficial.
1. Dynamin-related protein 1 as a regulatory protein of mitochondrial morphology and apoptosis in
breast cancer models
Gardner, Z., Hawley, K., Ramos, A., and Craig, K.J.
While breast cancer is the second most prevalent form of cancer, much about its tumorigenesis,
the conversion of a healthy cell to a cancerous cell, is poorly classified. Mitochondrial dynamics,
the process by which mitochondria undergo fusion and fission into longer and shorter
mitochondria may play a role in the development of breast cancer and remains largely
unclassified. As such, this study investigated the dynamic nature of mitochondria and its role in
breast cancer cells to examine the influence of mitochondrial fission on the intrinsic apoptosis
pathway. Mitochondrial fission is closely linked to the early steps of apoptosis in cell death
signaling. Translocation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1),
from the cytoplasm to the outer mitochondrial membrane begins apoptotic signaling in vitro.
Fission and permeabilization of the mitochondria is essential for the translocation pro-apoptotic
proteins from the mitochondria to the cytoplasm. Previous data in our lab showed that HTB-22
adenocarcinoma cells of the breast displayed a pro-fission phenotype when compared to the non-
tumorigenic HTB-125 breast epithelial cell controls. Further characterization of mitochondrial
length in a less invasive model, HTB-126 invasive ductal carcinoma, showed longer
mitochondrial lengths when compared to HTB-22 cells. The HTB-126 cells mimicked the
mitochondrial phenotype of the control HTB-125. DAPI staining observed via confocal
microscopy also revealed that neither HTB-125 nor HTB-126 cells displayed apoptotic
phenotypes as little to no nuclear fragmentation, a late-stage apoptotic marker, was visualized.
As all cancer cells exhibit apoptotic resistance in order to continue their proliferation, there will
be a point in the pathway by which the cancer cells dysregulate programmed cell death to
survive. The focus of this study was to examine the apoptotic pathway in HTB-22 cells
beginning with the characterization of the function of Drp1 in more detail, which is at the
beginning of the apoptotic pathway. Preliminary results suggest that more Drp1 translocates to
the outer mitochondrial membrane in HTB-22 cells when compared to the controls, which may
explain the morphology differences. After Drp1 initiates fission, cytochrome c leaves the
mitochondria and translocates to the cytoplasm to continue apoptotic signaling. Future work will
determine if cytochrome c or other downstream pro-apoptotic proteins are dysregulated to inhibit
apoptosis in the HTB-22 model of breast cancer. Expression of pro-apoptotic proteins will be
examined via immunocytochemistry using confocal microscopy and Western blotting to further
investigate the relationship between mitochondrial dynamics and apoptotic resistance in breast
cancer.