4 Binney Street

Boston, MA, United States

4 Binney Street

Boston, MA, United States

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Mehta S.,4 Binney Street | Huillard E.,Howard Hughes Medical Institute | Kesari S.,Dana-Farber Cancer Institute | Kesari S.,University of California at San Diego | And 10 more authors.
Cancer Cell | Year: 2011

High-grade gliomas are notoriously insensitive to radiation and genotoxic drugs. Paradoxically, the p53 gene is structurally intact in the majority of these tumors. Resistance to genotoxic modalities in p53-positive gliomas is generally attributed to attenuation of p53 functions by mutations of other components within the p53 signaling axis, such as p14 Arf, MDM2, and ATM, but this explanation is not entirely satisfactory. We show here that the central nervous system (CNS)-restricted transcription factor Olig2 affects a key posttranslational modification of p53 in both normal and malignant neural progenitors and thereby antagonizes the interaction of p53 with promoter elements of multiple target genes. In the absence of Olig2 function, even attenuated levels of p53 are adequate for biological responses to genotoxic damage. © 2011 Elsevier Inc.


Block S.D.,4 Binney Street
Epidemiologia e Psichiatria Sociale | Year: 2010

This article reviews common sources of suffering in patients with advanced illness, identifies challenges in appropriately diagnosing and treating depression in this setting, and examines the relationship between depression and other key clinical outcomes in the setting of advanced disease. A systematic literature review was conducted. Most of the existing research on patients with advanced illness has been conducted with cancer patients. Approximately 18 percent of patients with advanced illness meet criteria for major or minor depression; multiple psychiatric co-morbidities occur frequently. Prevalence rates increase as patients become sicker. However, depression is frequently underdiagnosed and undertreated in the setting of advanced illness. One of the key clinical challenges is differentiating depression from grief. Both psychosocial and psychopharmacologic interventions have been shown to be effective in treating depression in patients with advanced cancer. In conclusion, depression is a regular complication of advanced illness, reduces quality of life, compromises family member function, interferes with treatment decisions, and may shorten survival. However, numerous effective treatment approaches, including both medications and psychotherapy, exist and can be used to alleviate depression.


High-grade gliomas are notoriously insensitive to radiation and genotoxic drugs. Paradoxically, the p53 gene is structurally intact in the majority of these tumors. Resistance to genotoxic modalities in p53-positive gliomas is generally attributed to attenuation of p53 functions by mutations of other components within the p53 signaling axis, such as p14(Arf), MDM2, and ATM, but this explanation is not entirely satisfactory. We show here that the central nervous system (CNS)-restricted transcription factor Olig2 affects a key posttranslational modification of p53 in both normal and malignant neural progenitors and thereby antagonizes the interaction of p53 with promoter elements of multiple target genes. In the absence of Olig2 function, even attenuated levels of p53 are adequate for biological responses to genotoxic damage.

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