Penn Medicine recognizes March as Colorectal Cancer Awareness Month. Follow us all month for information on screening and prevention tips. 

Michele on her 2-year “cancerversary.”

At 50, Michele was feeling great. She’d done everything she was supposed to do to take care of her health.

Annual physical exam? Check.
Mammogram? Yup.
Echocardiogram? Done.
Skin check for moles and skin cancer? No problem.
Bone density scan? Of course.

But the one thing she’d put off was getting a colonoscopy.

“It was the only thing I hadn’t done, and I really didn’t think much of it,” remembers Michele. “I felt great; there wasn’t a reason to get one other than I was 50 and it was recommended I get one at 50.”

Two months before her 51st birthday, on Valentine’s Day, Michele had her colonoscopy in central New Jersey close to her home.

Her doctor found cancer. That colonoscopy saved her life.

“He told me he found lesions, and that I needed to see a specialist surgeon,” says Michele. “I left there dazed and confused.”

One week later, Michele met with Dr. Najjia Mahmoud, MD, Chief of the Division of Colon and Rectal Surgery in the Department of Surgery at Penn Medicine.

“Dr. Mahmoud had a calming effect,” says Michele. “She spoke to me in a way I could understand the process for my situation, she actually made it sound easy – and that put me at ease.”

It was stage 3 colon cancer, and after her surgery at Penn, Michele had 12 rounds of chemotherapy under the care of Ursina Teitelbaum, MD, medical oncologist at the Abramson Cancer Center.

“I was so impressed with Dr. Teitelbaum,” says Michele. “I walked into that first visit with two pages of questions, and she went through and answered each and every one.”

Michele got through those chemotherapy treatments, but it wasn’t an easy road.

“Chemotherapy was tough, but I got through it with the support of my friends and family, and the determination I had to get through it,” says Michele. “I walked every day – even if it was slow – because I knew that’s what I had to do.”

Today, Michele is cancer-free and is an advocate for colon cancer awareness. She’s participated in the Undy 5000 race, numerous awareness events, and supports multiple organizations through volunteer work. This year again, she had Governor Christie proclaim March, 2014, Colorectal Cancer Awareness Month in New Jersey.

“If I can save one person from being where I was, that makes me happy,” says Michele. “It’s estimated that 1 in 3 people are not up to date with their screenings, and that 1 in 20 will be diagnosed with colon cancer. Those numbers alone should alarm people to take action.”

Michele reminds us she had no symptoms of colon cancer – no pain, no blood in her stool, and her annual blood work was normal.

“I probably had colon cancer for years before I went for a screening,” she says, “but without the screening, I probably would have found out too late.”

Penn Medicine recognizes March as Colorectal Cancer Awareness Month. Follow us all month for information on screening and prevention tips. 

Michele on her 2-year “cancerversary.”

At 50, Michele was feeling great. She’d done everything she was supposed to do to take care of her health.

Annual physical exam? Check.
Mammogram? Yup.
Echocardiogram? Done.
Skin check for moles and skin cancer? No problem.
Bone density scan? Of course.

But the one thing she’d put off was getting a colonoscopy.

“It was the only thing I hadn’t done, and I really didn’t think much of it,” remembers Michele. “I felt great; there wasn’t a reason to get one other than I was 50 and it was recommended I get one at 50.”

Two months before her 51st birthday, on Valentine’s Day, Michele had her colonoscopy in central New Jersey close to her home.

Her doctor found cancer. That colonoscopy saved her life.

“He told me he found lesions, and that I needed to see a specialist surgeon,” says Michele. “I left there dazed and confused.”

One week later, Michele met with Dr. Najjia Mahmoud, MD, Chief of the Division of Colon and Rectal Surgery in the Department of Surgery at Penn Medicine.

“Dr. Mahmoud had a calming effect,” says Michele. “She spoke to me in a way I could understand the process for my situation, she actually made it sound easy – and that put me at ease.”

It was stage 3 colon cancer, and after her surgery at Penn, Michele had 12 rounds of chemotherapy under the care of Ursina Teitelbaum, MD, medical oncologist at the Abramson Cancer Center.

“I was so impressed with Dr. Teitelbaum,” says Michele. “I walked into that first visit with two pages of questions, and she went through and answered each and every one.”

Michele got through those chemotherapy treatments, but it wasn’t an easy road.

“Chemotherapy was tough, but I got through it with the support of my friends and family, and the determination I had to get through it,” says Michele. “I walked every day – even if it was slow – because I knew that’s what I had to do.”

Today, Michele is cancer-free and is an advocate for colon cancer awareness. She’s participated in the Undy 5000 race, numerous awareness events, and supports multiple organizations through volunteer work. This year again, she had Governor Christie proclaim March, 2014, Colorectal Cancer Awareness Month in New Jersey.

“If I can save one person from being where I was, that makes me happy,” says Michele. “It’s estimated that 1 in 3 people are not up to date with their screenings, and that 1 in 20 will be diagnosed with colon cancer. Those numbers alone should alarm people to take action.”

Michele reminds us she had no symptoms of colon cancer – no pain, no blood in her stool, and her annual blood work was normal.

“I probably had colon cancer for years before I went for a screening,” she says, “but without the screening, I probably would have found out too late.”

Epithelial-to-mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, miRNA, DNA methylation, and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma. The resulting data were integrated with functional profiles consisting of cell invasiveness, adhesion, and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. Other cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin-binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actin-binding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas. Cancer Res; 75(9); 1–12. ©2015 AACR.

Epithelial to mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, microRNA, DNA methylation and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma were integrated with functional profiles consisting of cell invasiveness, adhesion and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. However, most cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actin-binding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas.

The Notch pathway plays multiple key roles in tumorigenesis, and its signaling components have therefore aroused great interest as targets for emerging therapies. Here, we show that inhibition of Notch, using a soluble receptor Notch1 decoy, unexpectedly caused a remarkable increase in liver metastases from neuroblastoma and breast cancer cells. Increased liver metastases were also seen after treatment with the γ-secretase inhibitor PF-03084014. Transgenic mice with heterozygous loss of Notch1 demonstrated a marked increase in hepatic metastases, indicating that Notch1 signaling acts as metastatic suppressor in the liver microenvironment. Inhibition of DLL1/4 with ligand-specific Notch1 decoys increased sprouting of sinusoidal endothelial cells into micrometastases, thereby supporting early metastatic angiogenic growth. Inhibition of tumor-derived JAG1 signaling activated hepatic stellate cells, increasing their recruitment to vasculature of micrometastases, thereby supporting progression to macrometastases. These results demonstrate that inhibition of Notch causes pathologic activation of liver stromal cells, promoting angiogenesis and growth of hepatic metastases. Our findings have potentially serious implications for Notch inhibition therapy. Cancer Res; 75(8); 1–11. ©2015 AACR.