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Your search keyword '"Jain, Saloni"' showing total 2 results
Start Over Author "Jain, Saloni" Topic breast cancer
2 results on '"Jain, Saloni"'

1. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients.

Author

Tolaney, Sara M., Boucher, Yves, Duda, Dan G., Martin, John D., Seano, Giorgio, Ancukiewicz, Marek, Barry, William T., Goel, Shom, Lahdenrata, Johanna, Isakoff, Steven J., Yeh, Eren D., Jain, Saloni R., Golshan, Mehra, Brock, Jane, Snuderl, Matija, Winer, Eric P., Krop, Ian E., and Jain, Rakesh K.

Subjects
CANCER patients, COMEDO carcinoma, BREAST cancer, MEDICAL care, MEDICAL records
Abstract

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2- negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte- covered MVD, amarker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning. [ABSTRACT FROM AUTHOR]

Published
2015
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2. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels

Author

Chauhan, V. P., Martin, J. D., Liu, H., Lacorre, D. A., Jain, S. R., Kozin, S. V., Stylianopoulos, T., Mousa, A. S., Han, X., Adstamongkonkul, P., Popovic, Z., Huang, P., Bawendi, M. G., Boucher, Y., Jain, R. K., Stylianopoulos, T. [0000-0002-3093-1696], Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Chemistry, Martin, John Daniel, Jain, Saloni R., Popovic, Zoran, and Bawendi, Moungi G.

Subjects
decompression, Mechanotransduction, medicine.medical_treatment, transforming growth factor beta1, Mechanotransduction, Cellular, fluorouracil, Mice, stress, 0302 clinical medicine, Hyaluronic Acid, 0303 health sciences, Endothelin-1, Drug Synergism, Cell Hypoxia, 3. Good health, Gene Expression Regulation, Neoplastic, Losartan, 030220 oncology & carcinogenesis, Collagen, Type 1, medicine.medical_specialty, Antineoplastic Agents, doxorubicin, Article, perfusion, valsartan, General Biochemistry, Genetics and Molecular Biology, animal tissue, 03 medical and health sciences, candesartan, Interstitial matrix, Pancreatic cancer, cancer combination chemotherapy, Renin–angiotensin system, Humans, protein expression, mouse, drug potentiation, animal model, Drug Repositioning, Mechanical, medicine.disease, drug development, Pancreatic Neoplasms, Endocrinology, chemistry, vascular tumor, Stromal Cells, collagen, drug megadose, losartan, General Physics and Astronomy, chemotherapy, swelling, Angiotensin, chemistry.chemical_compound, hyaluronic acid, Hyaluronic acid, connective tissue growth factor, Multidisciplinary, lisinopril, article, female, Female, Fluorouracil, medicine.symptom, Receptor, medicine.drug, tumor, Angiotensins, Stromal cell, animal experiment, Biology, Receptor, Angiotensin, Type 1, Transforming Growth Factor beta1, Experimental, breast cancer, male, pancreas cancer, blood, Internal medicine, inhibition kinetics, drug mechanism, medicine, Animals, controlled study, 030304 developmental biology, Neoplastic, Chemotherapy, nonhuman, hypoxia, Mammary Neoplasms, Connective Tissue Growth Factor, Mammary Neoplasms, Experimental, General Chemistry, angiotensin receptor, Hypoxia (medical), disease treatment, Gene Expression Regulation, Cancer research, Stress, Mechanical, Cellular, Angiotensin II Type 1 Receptor Blockers, oxygen
Abstract

Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production, associated with decreased expression of profibrotic signals TGF-β1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition. Consequently, losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism, losartan improves drug and oxygen delivery to tumours, thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors—inexpensive drugs with decades of safe use—could be rapidly repurposed as cancer therapeutics., National Cancer Institute (U.S.) (Grant P01-CA080124), National Cancer Institute (U.S.) (Grant R01-CA126642), National Cancer Institute (U.S.) (Grant R01-CA085140), National Cancer Institute (U.S.) (Grant R01-CA115767), National Cancer Institute (U.S.) (Grant R01-CA098706), United States. Dept. of Defense. Breast Cancer Research Program (Innovator Award W81XWH-10-1-0016), Lustgarten Foundation (Dana-Farber Cancer Institute/David H. Koch Institute for Integrative Cancer Research at MIT Bridge Project Grant)

Published
2013
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