Previous Page  28 / 36 Next Page
Information
Show Menu
Previous Page 28 / 36 Next Page
Page Background

Volume 2, Issue 3(Suppl)

Oncol Cancer Case Rep

ISSN: 2471-8556 an open access journal

Page 59

Notes:

Cancer Therapy & Biomarkers 2016

December 05-07, 2016

conferenceseries

.com

CANCER THERAPY,

BIOMARKERS & CLINICAL RESEARCH

15

th

World Congress on

December 05-07, 2016 Philadelphia, USA

Gut microbiota modulates cisplatin mediated systemic toxicity

Soumen Roy

1

, Rodrigo Das Neves

1

, Carolyne Smith

1

, Bathai Edwards

1

, Amiran Dzutsev

1

, Loretta Smith

2

, Simone Difilippantonio

2

, Lake Ross

3

, Susan

Garfield

4

, Poonam Mannan

4

, Lim Langston

4

, Hawes Misty

2

, Ren Ming Dai

1

, Sharon Bargo

1

, Young Kim

and

Giorgio Trinchieri

1

,

2

1

Cancer and Inflammation Program, NCI, NIH, USA

2

Cancer and Inflammation Program, NCI, NIH, USA

3

Laboratory of Genitourinary Cancer Pathogenesis, NCI, USA

4

Confocal Core, CCR, NCI, NIH, USA

5

Division of Cancer prevention, NCI, NIH, USA

Anticancer chemotherapy has achieved a significant milestone in increasing the number of cancer survivors over past decades,

while leaving behind the survivors with various toxic side effects, which are nephrotoxicity, ototoxicity and intestinal damage.

Challenges remain to reduce systemic toxicity as well as retaining the anticancer therapy. Gut microbiota modulates cancer

chemotherapy, however little is known about the role of gut microbiota in modulating systemic toxicity. We hypothesized that

gut microbiota regulates systemic toxicity. Four groups (n=10/group) of 8 weeks old C57B/6 mice were treated with cisplatin,

cisplatin+antibiotics cocktails (ABX), ABX only and untreated. ABX cocktail contained primaxin, vancomycin and neomycin,

which depletes broad spectrum gut microbiota. This experiment was validated using C57B/6 germ free mice (contains no

microorganisms). We performed anti-p-γ-H2AX and anti-ATM based DNA-double stranded break (stains foci in the nuclei)

based toxicity assay in kidney and gut (small bowel). H&E and 4 color immunostaining (anti-p-γ-H2AX, anti-ATM, Actin and

DAPI) were done. DNA-DSBs were evaluated using Zeiss 780 confocal and quantified by 3-D reconstruction using IMARIS.

There were reductions in γ-H2AX

+

DAPI

+

(DNA damaged) cell populations compared to only cisplatin treated mice, indicated

protection in the kidney. Both nuclear foci counts as well as the pathological scores indicated gut microbiota associated modu-

lation in the glomeruli of kidney and in the villi of small bowel. Our data leads to a possibility to develop microbiota based ther-

apy which might be utilized to reduce chemotherapy associated systemic toxicity and for better management of chemotherapy.

Biography

Roy is currently working in the field of cancer and gut microbiota at the National Cancer Institute (NCI), NIH in the laboratory of Dr. Giorgio Trinchieri. His main focus

is to investigate the role of gut microbiota in chemotherapeutic drug and radiation therapy induced local and systemic toxicity. Prior joining the National Cancer

Institute, Dr. Roy worked at the National Institutes on Deafness and other Communication Disorders (NIDCD) in the Laboratory of Dr. Lisa Cunningham, where he

contributed to the development of a sound conditioning based co-therapy, which inhibits cisplatin and aminoglycoside mediated hearing loss in mice. Roy received

his doctorate degree under the supervision of Anneliese Schrott Fischer in the field of targeted nanomedicine and hearing from University of Innsbruck, Austria in

2011

soumen.roy@nih.gov boxellj@mail.nih.gov

Soumen Roy et al., Oncol Cancer Case Rep 2016,2:3(Suppl)

http://dx.doi.org/10.4172/2471-8556.C1.002