BI-03 * DLX HOMEOBOX GENES REGULATE NEURONAL VS OLIGODENDROGLIAL CELL FATE DECISIONS: POTENTIAL RELEVANCE TO PEDIATRIC GLIONEURONAL TUMORS AND HIGH GRADE GLIOMAS

Homeobox genes control body patterning and cell-fate decisions during development. The homeobox genes consist of many families, only some of which have been investigated regarding a possible role in tumorigenesis. Dysregulation of HOX family genes have been widely implicated in cancer etiology. DLX homeobox genes, which belong to the NK-like family, exert dual roles in development and cancer. The DLX genes are the key transcription factors involved in regulating the development of craniofacial structures in vertebrates. The three DLX bigenes have overlapping expression in the branchial arches. Disruption of DLX function has destructive consequences in organogenesis and is associated with certain congenital disorders in humans. The role of DLX genes in oncogenesis is only beginning to emerge. DLX2 diminishes cellular senescence by regulating p53 function, whereas DLX4 has been associated with metastasis in breast cancer. In human ovarian cancer cells, DLX5 is essential for regulating AKT signaling, thereby promoting cell proliferation and survival. We previously implicated Dlx5 as an oncogene in murine T-cell lymphoma driven by a constitutively active form of Akt2. In this mouse model, overexpression of Dlx5 was caused by a chromosomal rearrangement that juxtaposed the Tcr-beta promoter region near the Dlx5 locus. Moreover, transgenic mice overexpressing Dlx5, specifically in immature T-cells, develop spontaneous thymic lymphomas. Oncogenesis in this mouse model involves binding of Dlx5 to the Notch1 and Notch3 gene loci to activate their transcription. Dlx5 also cooperates with Akt signaling to accelerate lymphomagenesis by activating Wnt signaling. We also discuss the fact that human DLX5 is aberrantly expressed in several human malignancies.

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Cellular senescence is a central response to cytotoxic chemotherapy in high-grade serous ovarian cancer

10.1101/425199 ◽

2018 ◽

Cited By ~ 5

Author(s):

L. Calvo ◽

S. Cheng ◽

M. Skulimowski ◽

I. Clément ◽

L. Portelance ◽

...

Keyword(s):

Ovarian Cancer ◽

Dna Damage ◽

Cell Fate ◽

Cellular Senescence ◽

Response To Treatment ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cell Fate Decisions ◽

Response To Chemotherapy

AbstractHigh-grade serous ovarian cancer (HGSOC) commonly responds to initial therapy, but this response is rarely durable. Understanding cell fate decisions taken by HGSOC cells in response to treatment could guide new therapeutic opportunities. Here we find that primary HGSOC cultures undergo therapy-induced senescence (TIS) in response to DNA damage induced by chemotherapy. HGSOC-TIS displays most senescence hallmarks including persistent DNA damage, senescence-associated inflammatory secretome, and selective sensitivity to senolytic Bcl-2 family inhibitors, suggesting avenues for preferential synergistic clearance of these cells. Comparison of pre- and post-chemotherapy HGSOC patient tissue samples revealed changes in senescence biomarkers suggestive of post-treatment “in patient” TIS, and a stronger TIS response in post-chemotherapy tissues correlated with better 5-year survival rates for patients. Together, these data suggest that the induction of cellular senescence in HGSOC cells accounts at least in part for beneficial cellular responses to treatment in patients providing a new therapeutic target.One Sentence SummaryCellular senescence is a central beneficial response to chemotherapy in high-grade serous ovarian cancer bothin vitroand in patient.

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Hypofractionated Stereotactic Radiation Therapy: An Effective Therapy for Recurrent High-Grade Gliomas

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2011.04.049 ◽

2011 ◽

Vol 2011 ◽

pp. 137-138

Author(s):

J. Uhm

Keyword(s):

Radiation Therapy ◽

Effective Therapy ◽

High Grade ◽

Stereotactic Radiation Therapy ◽

Stereotactic Radiation ◽

High Grade Gliomas

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Venous Thromboembolism and High Grade Gliomas

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649592 ◽

1993 ◽

Vol 70 (03) ◽

pp. 393-396 ◽

Cited By ~ 38

Author(s):

Mandeep S Dhami ◽

Robert D Bona ◽

John A Calogero ◽

Richard M Hellman

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Medical Center ◽

Significant Risk ◽

Bleeding Complications ◽

Fisher Exact Test ◽

High Grade ◽

Chi Square ◽

Exact Test ◽

High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

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