Page 306 - 2014 Printable Abstract Book
P. 306
values close to their mean as one of their elements. Since in this such research it is the mean value of
these triples that is of specific interest, an investigator wishing to guide the results of his investigations,
might well be inclined to invent triples by choosing a near mean value as one of the elements, and
numbers equidistant on either side as the two others. When simple links to spreadsheets containing data
triples in adjacent columns are set up, our Excel spreadsheet: 1) tabulates frequencies of terminal digit
data values; 2) counts the number of data values that have duplicated terminal digits; and 3) counts the
number of triples that contain their mean or a near mean value, and applies appropriate statistical tests
to identify data anomalies. Screening using a spreadsheet of this type could help to further minimize data
fabrication and falsification and elevate statistics to its rightful place in the armamentarium of fraud-
detecting software.
(PS5-33) A novel neu-positive mammary tumor model for studies of metastatic breast cancer treatment.
Peigen Huang, MD, MSc; Wende Li, MD, MSc; Yuhui Huang, PhD; Yujiao Liu, BS; Rakesh Ramjiawan, MS;
Xiaoxing Han, PhD; Dai Fukumura, MD, PhD; Dan G. Duda, DMD, PhD; and Rakesh K. Jain, PhD;
Massachusetts General Hospital/Harvard Medical School, Boston, MA
Improving the response of HER2/Neu-positive metastatic breast cancer to multimodal treatments
is urgently needed. To this end, we established a novel Neu-positive (Neu+) metastatic mammary tumor
model named MCa-M3C. We first implanted spontaneous mammary adenocarcinoma tissue arising in a
female MMTV-PyVT/FVB transgenic mouse into the mammary fat pads (MFP) of FVB mice. Subsequently,
the breast cancer metastases in the lungs of these FVB hosts were re-implanted into MFP of other
recipients. Following 3 serial selections of breast cancer metastasis to the lung from this tumor-MFP
implantation, a fresh lung metastatic tumor tissue was obtained and successfully cultured in vitro as a
long-term passage monolayer cell line. The cell line showed a stable cell doubling time (25.3 ± 4.4 h), high
platting efficiency (0.43 ± 0.04), and resistance to irradiation by clonogenic assay when compared to the
MCa-PSTC, a non-selected cell line was established from a primary mammary tumor that arose in a MMTV-
5
PyVT/FVB mouse. MCa-M3C cells showed high in vivo tumorigenicity: 10 -cell injections into MFP led to a
100% tumor take rate. These tumors have been transplanted serially by orthotopic MFP implantations for
up to 4 passages with 100% implantability. Spontaneous lung metastases were detected in about 75% of
mice within 2-4 months after removal of primary MFP tumors at a size of 10 x 10 mm. Histological
examination showed that MFP tumors and their lung metastases retained the histological features of
adenocarcinomas. In addition, both the cells and their tumor tissues showed strong Neu+ expression by
Western blot. Tumors also presented high collagen density in their stromal as detected by Masson’s
Trichrome staining. Thus, we combined anti-fibrotic treatment using the angiotensin receptor blocker
losartan with ionizing radiotherapy (L+IR) in this MCa-M3C MFP implanted model. Following a 7–day
treatment with losartan, 40 mg/kg body weight, gauvaged daily, a 25 Gy single dose local IR was given.
Results show that L+IR significantly reduced the tumor volume (by about 40%) when compared to IR alone
(p=0.0002). In summary, we have established a new model of aggressive Neu+ breast cancer and have
used it to test a combining losartan and radiotherapy. Our preliminary results clearly show that L+IR
additively inhibited MCa-M3C tumor growth.
304 | P a g e
these triples that is of specific interest, an investigator wishing to guide the results of his investigations,
might well be inclined to invent triples by choosing a near mean value as one of the elements, and
numbers equidistant on either side as the two others. When simple links to spreadsheets containing data
triples in adjacent columns are set up, our Excel spreadsheet: 1) tabulates frequencies of terminal digit
data values; 2) counts the number of data values that have duplicated terminal digits; and 3) counts the
number of triples that contain their mean or a near mean value, and applies appropriate statistical tests
to identify data anomalies. Screening using a spreadsheet of this type could help to further minimize data
fabrication and falsification and elevate statistics to its rightful place in the armamentarium of fraud-
detecting software.
(PS5-33) A novel neu-positive mammary tumor model for studies of metastatic breast cancer treatment.
Peigen Huang, MD, MSc; Wende Li, MD, MSc; Yuhui Huang, PhD; Yujiao Liu, BS; Rakesh Ramjiawan, MS;
Xiaoxing Han, PhD; Dai Fukumura, MD, PhD; Dan G. Duda, DMD, PhD; and Rakesh K. Jain, PhD;
Massachusetts General Hospital/Harvard Medical School, Boston, MA
Improving the response of HER2/Neu-positive metastatic breast cancer to multimodal treatments
is urgently needed. To this end, we established a novel Neu-positive (Neu+) metastatic mammary tumor
model named MCa-M3C. We first implanted spontaneous mammary adenocarcinoma tissue arising in a
female MMTV-PyVT/FVB transgenic mouse into the mammary fat pads (MFP) of FVB mice. Subsequently,
the breast cancer metastases in the lungs of these FVB hosts were re-implanted into MFP of other
recipients. Following 3 serial selections of breast cancer metastasis to the lung from this tumor-MFP
implantation, a fresh lung metastatic tumor tissue was obtained and successfully cultured in vitro as a
long-term passage monolayer cell line. The cell line showed a stable cell doubling time (25.3 ± 4.4 h), high
platting efficiency (0.43 ± 0.04), and resistance to irradiation by clonogenic assay when compared to the
MCa-PSTC, a non-selected cell line was established from a primary mammary tumor that arose in a MMTV-
5
PyVT/FVB mouse. MCa-M3C cells showed high in vivo tumorigenicity: 10 -cell injections into MFP led to a
100% tumor take rate. These tumors have been transplanted serially by orthotopic MFP implantations for
up to 4 passages with 100% implantability. Spontaneous lung metastases were detected in about 75% of
mice within 2-4 months after removal of primary MFP tumors at a size of 10 x 10 mm. Histological
examination showed that MFP tumors and their lung metastases retained the histological features of
adenocarcinomas. In addition, both the cells and their tumor tissues showed strong Neu+ expression by
Western blot. Tumors also presented high collagen density in their stromal as detected by Masson’s
Trichrome staining. Thus, we combined anti-fibrotic treatment using the angiotensin receptor blocker
losartan with ionizing radiotherapy (L+IR) in this MCa-M3C MFP implanted model. Following a 7–day
treatment with losartan, 40 mg/kg body weight, gauvaged daily, a 25 Gy single dose local IR was given.
Results show that L+IR significantly reduced the tumor volume (by about 40%) when compared to IR alone
(p=0.0002). In summary, we have established a new model of aggressive Neu+ breast cancer and have
used it to test a combining losartan and radiotherapy. Our preliminary results clearly show that L+IR
additively inhibited MCa-M3C tumor growth.
304 | P a g e
