Yearly Archives: 2007

Nanotechnology used to differentiate metastatic cancer cells from normal cells

  • 12/31/2007
  • web-based article
  • Lisa Martin

A multidisciplinary team of UCLA scientists were able to differentiate metastatic cancer cells from normal cells in patient samples using leading-edge nanotechnology that measures the softness of the cells.

The study represents one of the first times researchers have been able to take living cells from cancer patients and apply nanotechnology to analyze them and determine which were cancerous and which were not. The nano science measurements may provide a potential new method for detecting cancer, especially in cells from body cavity fluids where diagnosis using current methods is typically very challenging. The method also may aid in personalizing treatments for patients.

When cancer is becoming metastatic, or invading other organs, the diseased cells must travel throughout the body. Because the cells need to enter the bloodstream and maneuver through tight anatomical spaces, cancer cells are much more flexible, or softer, than normal cells. These spreading, invading cancer cells can cause a build-up of fluids in body cavities such as the chest and abdomen. But fluid build-up in patients does not always mean cancer cells are present. If the fluid could be quickly and accurately tested for the presence of cancer, oncologists could make better decisions about how aggressive a treatment should be administered or if any treatment is necessary at all.

In this study, researchers collected fluid from the chest cavities of patients with lung, breast and pancreatic cancers, a relatively non-invasive procedure. One problem with diagnosing metastatic disease in this setting is that cancer cells and normal cells in body cavity fluids look very similar under an optical microscope, said Jianyu Rao, a researcher at UCLA’s Jonsson Cancer Center, an associate professor of pathology and laboratory medicine and one of the study’s senior authors. Conventional diagnostic methods detect about 70 percent of cases where cancer cells are present in the fluid, missing about 30 percent of cases.

“We detect cancer cells typically by looking at them under a microscope after the cells are fixed and stained with chemicals, which is really an antiquated method,” Rao said. “Usually the cancer cells have larger nuclei and other subtle features. However, the normal cells from body cavity fluids can look almost identical to cancer cells under an optical microscope. While staining for tumor protein markers could increase diagnostic accuracy, what we were missing was a way to determine if cancer cells have different mechanical properties than normal cells.”

Employing one of the most valuable tools in the nanotechnology arsenal, the research team used an Atomic Force Microscope (AFM) to measure cell softness. Since the cells being analyzed were less than half the diameter of a human hair, researchers needed a very precise and delicate instrument to measure resistance in the cell membrane, said James Gimzewski, professor of chemistry and biochemistry, a member of the California NanoSystems Institute and also one of the study’s senior authors.

“We had to measure the softness of the cell without bursting it,” Gimzewski said. “Otherwise, it’s like trying to measure the softness of a tomato using a hammer.”

The AFM uses a minute, sharp tip on a spring to push against the cell surface and determine the degree of softness. Think of it as an extension of a doctor’s hands performing a physical examination to determine disease, Gimzewski said.

“You look at two tomatoes in the supermarket and both are red. One is rotten, but it looks normal,” Gimzewski said. “If you pick up the tomatoes and feel them, it’s easy to figure out which one is rotten. We’re doing the same thing. We’re poking and quantitatively measuring the softness of the cells.”

After probing a cell, the AFM assigns a value that represents how soft a cell is based on the resistance encountered. What the team found was that the cancer cells were much softer than the normal cells and they were similarly soft with very little variation in gradation. The normal, healthy cells from the same specimen were much stiffer than the cancer cells and, in fact, the softness values assigned to each group did not overlap at all, making diagnosis using this nanomechanical measurement easier and more accurate.

“It was fascinating to find such striking characteristics between the metastatic cancer cells and normal cells,” said Sarah Cross, a graduate student in the chemistry and biochemistry department and a study author. “The metastatic cancer cells were extremely soft and easily distinguishable from the normal cells despite similarities in appearance. And we’re looking at live cells taken from human patients, so that makes this is a unique finding.”

Calvin Quate of Stanford University, the co-inventor of the Atomic Force Microscope, said the UCLA study breaks new ground.

“This manuscript is the first that directly shows a relationship between the nanomechanical properties and physiological function in clinical samples from patients with suspected cancer,” said Quate, 1992 Medal of Science recipient.

National breast cancer expert Susan Love said the study findings “open a new era for function-based tumor cell diagnostics.”

“With these findings, it is foreseeable that a combined biochemical, biophysical and morphological analysis for analyzing human cytological specimens using AFM may be finally realized,” said Love, president and medical director of the Susan Love Research Foundation and a clinical professor of surgery at UCLA.

Researchers next will explore whether the nanomechanical analysis can be used to personalize cancer treatment based on the characteristics of a patient’s cancer cells. There are standard chemotherapy drugs that are used to treat metastatic cancer, Rao said, but response varies from patient to patient. If researchers could test the cancer cells beforehand, they could potentially apply therapies that would make the cells stiffer, making it more difficult for the diseased cells to spread through the body.

This research was published Dec. 2, 2007 in the advance online edition of the journal Nature Nanotechnology,

The study was a collaboration between the California NanoSystems Institute, the Jonsson Cancer Center and the Departments of Chemistry and Biochemistry and Pathology and Laboratory Medicine. In addition to Rao, Gimzewski and Cross, the research team included Yu-Sheng Jin.

December, 2007|Archive|

Use of External Beam Radiotherapy is Associated with Reduced Incidence of Second Primary Head and Neck Cancer: A SEER Database Analysis

  • 12/31/2007
  • Aurora, CO
  • Kyle Rusthoven et al.
  • Int J Radiat Oncol Biol Phys, December 8, 2007

Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA).

Methods and Materials:
The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined and compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA.

Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91).

For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.

December, 2007|Archive|

Mitochondrial resequencing arrays detect tumor-specific mutations in salivary rinses of patients with head and neck cancer

  • 12/31/2007
  • Baltimore, MD
  • SK Mithani et al.
  • Clin. Cancer Res., December 15, 2007; 13(24): 7335-40

Alterations of the mitochondrial genome have been identified in multiple solid tumors and in many head and neck squamous cell carcinomas (HNSCC). Identification of mitochondrial mutations in the salivary rinses of patients with HNSCC has potential application in disease detection. In this study, we used the MitoChip v2.0 mitochondrial genome resequencing array to detect minor populations of mitochondrial DNA in salivary rinses of patients with HNSCC.

Experimental Design:
Salivary rinses from 13 patients with HNSCC, whose tumors carried mitochondrial mutations, were collected before surgical resection. DNA isolated from salivary rinses and serial dilutions of DNA derived from HNSCC-derived cell lines with known mitochondrial mutations were sequenced using the MitoChip, and analyzed using a quantitative algorithm which we developed to detect minor populations of mitochondrial DNA from MitoChip probe intensity data.

We detected heteroplasmic populations of mitochondrial DNA up to a 1:200 dilution using MitoChip v2.0 and our analysis algorithm. A logarithmic relationship between the magnitude of assay intensity and concentration of minor mitochondrial populations was shown. This technique was able to identify tumor-specific mitochondrial mutations in salivary rinses from 10 of 13 (76.9%) patients with head and neck cancer.

Minor populations of mitochondrial DNA and disease-specific mitochondrial mutations in salivary rinses of patients with HNSCC can be successfully identified using the MitoChip resequencing array and the algorithm which we have developed. This technique has potential application in the surveillance of patients after resection and may have applicability in the surveillance of body fluids in other tumor types.

SK Mithani, IM Smith, S Zhou, A Gray, WM Koch, A Maitra, and JA Califano

Authors’ affiliation:
Department of Surgery, Division of Plastic and Reconstructive Surgery, Department of Otolaryngology-Head and Neck Surgery, and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland.

December, 2007|Archive|

Aspiration in chemoradiated patients with head and neck cancer

  • 12/31/2007
  • Chicago, IL
  • A Langerman et al.
  • Arch Otolaryngol Head Neck Surg, December 1, 2007; 133(12): 1289-95

To review the incidence of aspiration after chemoradiation therapy in patients with head and neck cancer (HNC).

Retrospective review.

Academic institution.

One hundred thirty patients with advanced HNC underwent chemoradiation therapy at our institution between 1998 and 2002 as part of a larger, multi-institutional, prospective study of induction chemotherapy followed by chemoradiation therapy; the 118 patients (91%) for whom oropharyngeal motility (OPM) study data were available are discussed in this article.

Main Outcome Measures:
Incidence of trace ( 5%) aspiration (deep laryngeal or tracheal penetration) as determined by pretreatment and posttreatment OPM studies and correlation of the findings with the patients’ reported symptoms.

Eighty-one patients (69%) underwent at least 1 OPM study demonstrating aspiration within the first year after chemoradiation therapy, with 30 (25%) demonstrating frank aspiration. Of the patients who aspirated, 61 (75%) reported no symptoms of coughing or choking (80% of trace and 67% of frank aspirators). The patients with cancer of the larynx and hypopharynx were more likely to be aspirators (P = .007 and P = .004, respectively). Of the 62 patients with available pretreatment OPM data, 33 (53%) demonstrated aspiration at baseline.

Aspiration is highly prevalent among patients with advanced HNC at baseline and is worse in the posttreatment period after chemoradiation therapy. The majority of these patients report no symptoms. All patients with advanced HNC should undergo instrumental swallow assessment, even in the absence of symptoms, to detect subclinical aspiration and to institute therapeutic maneuvers and swallow precautions as well as to determine the safety of oral feeding.

A Langerman, E Maccracken, K Kasza, DJ Haraf, EE Vokes, and KM Stenson

Authors’ affiliation:
Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, 5841 S Maryland Ave, MC1035, Chicago, IL 60637

December, 2007|Archive|

Major Clinical Cancer Advances in 2007

  • 12/28/2007
  • web-based article
  • Zosia Chustecka

This past year had 6 major clinical cancer advances and a further 18 that are considered “notable,” according to the American Society of Clinical Oncology (ASCO) in its independent annual review. The report, Clinical Cancer Advances 2007, has been published online December 17 in the Journal of Clinical Oncology.

In the report, ASCO officials review what they consider to be the most significant cancer research presented or published over the past year, much of which has already been reported in news articles on Medscape Oncology. Together, these advances demonstrate “the important progress being made on the front lines of clinical cancer research today,” says ASCO president Nancy Davidson, MD.

ASCO lists the following as major advances:

= Magnetic resonance imaging for breast cancer screening.
– The role of human papilloma virus in head and neck cancers.
– Decreasing use of hormone replacement therapy linked to declines in breast cancer cases.
– Preventive radiation therapy improves survival and decreases brain metastases in patients with advanced small-cell lung cancer.
– Sorafenib (Nexavar, Onyx/Bayer) improves survival in liver cancer.
= Bevacizumab (Avastin, Genentech/Roche) improves treatment of advanced kidney cancer. The report notes that in recent years, 3 new agents have been approved for kidney cancer — sorafenib, sunitinib (Sutent, Pfizer), and temsirolimus (Torisel, Wyeth) — and future trials will need to compare bevacizumab with these agents and explore combinations.

The following are considered to be “notable” advances:
– Arsenic trioxide (Trisenox, Cell Therapeutics Inc) improves leukemia survival.
– Dasatinib (Sprycel, Bristol-Myers Squibb) active as first-line treatment for chronic myelogenous leukemia.
– Lenalidomide (Revlimid, Celgene Corp) and bortezomib (Velcade, Ortho-Biotech) more effective together for myeloma.
– Hypofractionated radiation (fewer but larger doses) appears to be as effective as standard-dose radiation in early-stage breast cancer.
– Bevacizumab with irinotecan (Camptosar, Pfizer) effective against gliomas.
– Radiotherapy improves survival of elderly patients with glioblastomas.
– Cetuximab (Erbitux, ImClone Systems) improves outcomes in colon cancer when added onto the FOLFIRI regimen (fluorouracil, irinotecan, and leucovorin).
– High-fat diets linked to recurrence of colon cancer.
External-beam radiation does not improve outcomes in endometrial cancer.
– Cetuximab with chemotherapy as first-line treatment prolongs survival in head and neck cancers.
– Investigational drug axitinib (under development by Pfizer) shows activity against advanced thyroid cancer.
– Less intense treatment for children with neuroblastoma achieves high survival rates.
– Small investments can improve childhood cancer treatment in low- and middle-income countries.
– Imatinib (Gleevec, Novartis) increases recurrence-free survival in patients with gastrointestinal stromal tumors.
– Aspirin use promising for prevention of colorectal cancer.
– Long-term health problems in survivors of childhood cancers.
– Survivors of childhood leukemia and brain tumors have elevated stroke risk.
– Most survivors of childhood cancer do not get recommended follow-up care.

J Clin Oncol. Published online December 17, 2007.

December, 2007|Archive|

Infrared Camera Might Predict, Prevent Complications in Patients with Head and Neck CA

  • 12/28/2007
  • San Francisco, CA
  • staff

Radiation-induced oral mucositis is the most common complication observed in patients with head and neck cancer who underwent radiation therapy. Thanks to a newly developed supersensitive infrared camera from Argonne National Laboratory, early diagnosis and possible prevention and/or treatment of oral mucositis could be possible:

While buccal and other head-and-neck cancers are treatable and frequently curable, patients who undergo the necessary treatment regimen — a combination of radiation and chemotherapy — frequently develop unpleasant side effects. One of the most common and painful of these, oral mucositis, involves the inflammation and ulceration of the mucous membranes of the mouth and soft palate. These sores can make speaking, eating or even opening the mouth extraordinarily painful. If patients experience especially severe toxicity, they may temporarily lose the ability to taste or may even need to be fed through a tube…

As part of the ongoing National Cancer Initiative, researchers at the U.S. Department of Energy’s Argonne National Laboratory have teamed up with oncologists at the University of Chicago to use infrared imaging of the head and neck to predict which patients have the highest risk for severe mucositis. Patients who show local increases in temperature around the tumor site in the immediate wake of the initial round of treatment may be more likely to suffer later side effects, said Ezra Cohen, a University of Chicago oncologist who will head up the clinical side of the project.

Cohen, in collaboration with Valentyn Novosad, a principal investigator in Argonne’s Materials Science Division (MSD), has already run a pilot study of six patient volunteers, which they parlayed into a successful grant proposal to the National Institutes of Health that will enable them to undertake a two-year study of 34 patients with head and neck cancers.

Oncologists use radiation therapy as an aggressive, but crude, method for fighting cancer. Although the radiation beam is typically focused on the area that contains the tumor, it cannot tell the difference between healthy and malignant cells. As a result, normal tissues suffer collateral damage as tumors are zapped. “At this point,” Cohen said, “we have no treatment that allows us to kill tumor cells without also damaging normal tissue. We accept the toxicity because it’s a necessary part of the intended cure, and we know that it eventually gets better…”

In order to detect possible toxicity, Novosad and Argonne physicist Volodymyr Yefremenko developed a prototype infrared camera that detects temperature gradations as small as one-twentieth of a degree Celsius. Typically, the tumor appears warmer than the surrounding tissue, but for some patients the infrared image taken after the first round of chemo- or radiation therapy shows a larger region of elevated temperature around the tumor site, indicating the beginning stages of inflammation. These patients, Cohen said, are the ones most likely to encounter problems with mucositis down the road, even if they are not yet symptomatic. Argonne scientists are developing a standardized approach to quantify changes in thermal signature of individual patients during the course of therapy…

Without this technology, doctors would have no way of telling which patients had the greatest risk for developing mucositis, Cohen said. “Right now, I can only say to a patient that there is a small chance of severe toxicity, a good chance of moderate toxicity, and a small chance of very little toxicity. The problem has been that we’ve had no way to predict upfront who will suffer the most.”

If doctors can use this technology to detect that a patient is likely to suffer a great deal of toxicity, it may enable them to tailor their treatment regimens more closely to patients’ individual needs, according to Cohen. “If I knew that a patient would encounter severe toxicity, I might want to reduce the doses of chemotherapy a little bit. Or I might want to put in a feeding tube early on knowing that they’re going to have trouble eating and drinking down the road. Or I might want to have very early consultations with physical therapists knowing that these are patients who are going to have trouble.”

December, 2007|Archive|

Expanding Role of the Medical Oncologist in the Management of Head and Neck Cancer

  • 12/25/2007
  • web-based article
  • Nicholas Choong, MD and Everett Vokes, MD
  • CA Cancer J Clin 2007

The multidisciplinary approach to treating squamous cell carcinoma of the head and neck is complex and evolving. This article aims to review some recent developments in squamous cell carcinoma of the head and neck, in particular the expanding role of chemotherapy in its management. Surgery and radiotherapy have remained the mainstay of therapy. Chemotherapy is increasingly being incorporated into the treatment of squamous cell carcinoma of the head and neck. Previously, radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced resectable disease. Data from randomized trials have confirmed the benefits of concurrent chemoradiotherapy in the adjuvant setting. Chemoradiotherapy is also the recommended approach for unresectable disease. Induction chemotherapy has been useful in resectable disease where organ preservation is desirable, but this approach was inferior for the goal of larynx preservation, while leading to similar survival when compared with concomitant chemoradiotherapy. There is recent evidence that taxanes added to induction chemotherapy with cisplatin and fluorouracil result in improved survival outcomes. Novel targeted agents, such as epidermal growth factor receptor antagonists, are showing promise in the treatment of patients with both locoregionally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck.

December, 2007|Archive|

Gold helps in cancer fight

  • 12/25/2007
  • London, England
  • staff

Cancerous tumours can be detected under the skin by using tiny gold particles embedded with dyes, a new study claims.

Scientists at Emory University and the Georgia Institute of Technology said the new technique could one day help doctors to detect and diagnose cancer earlier and less invasively.

The researchers injected mice with gold particles studded with antibody fragments called ScFv peptides that bind cancer cells.

They found that the particles grab on to tumours, and when illuminated with a laser beam they send back a signal that is specific to the dye.

Writing in the journal Nature Biotechnology, the scientists say the cancer cells were detected at a depth of 1cm to 2cm, making the gold particles an especially appropriate tool for head and neck tumours that tend to be more accessible.

They argue that the treatment will need further adaptation before it can be used for lung or abdominal cancers deep within the body.

The gold particles are extremely bright and are about 60 to 80 nanometres in diameter – thousands of times smaller than a human hair.

“I expect that with these probes it will be possible to detect cancer much earlier, at the microscopic level,” said Dr Dong Moon Shin, associate director of Emory’s Winship Cancer Institute.

“Even a half-centimetre-wide nodule contains millions of cancer cells, but with this technology we can detect many fewer cells at a time.”

The researchers now plan to modify the coatings of the nanoparticles to improve tumour targeting. They hope that the gold particles could also be used to selectively deliver drugs to cancer cells.

December, 2007|Archive|

Santa Treated for Throat Cancer

  • 12/25/2007
  • KSPR News
  • KSPR-ABC (

Remember the story “Rudolph the Red-Nosed Reindeer?”

When bad weather almost stopped Santa from delivering gifts on Christmas Eve? Well, the same thing almost happened to the Santa you’re about to meet. But instead of dealing with bad weather, this Santa faced an even bigger problem. Throat cancer.

And just as the legendary light from that story guided Santa through the storm, a laser light helped this Santa weather the storm of cancer.

“I don’t think there’s anything more satisfying – you feel so blessed – than giving,” this Santa says.

And this Santa says he was given the gift of life when doctors at Mayo Clinic found and removed a cancerous tumor from the base of his tongue. But treatment wasn’t easy.

“These cancers and the treatments for them interfere with a lot of things we take for granted. From breathing to speaking to eating to our appearance,” says Dr. Michael Hinni, a Mayo Clinic surgeon.

Dr. Hinni says that’s because the tumors are often hard to reach. Surgery can be disfiguring, chemo is very toxic and radiation can damage other structures in your throat. But now, new CO2 laser technology that bounces light energy off mirrors is making treatment easier for some patients. First, doctors guide the flexible fiber through the mouth to the tumor. The fiber is lined with many layers of tiny mirrors. These mirrors bounce the laser energy in any direction – even around corners.

“That allows us to access tumors that we couldn’t quite get to before,” says Hinni.

The technology allowed Santa to avoid toxic chemotherapy. Still, recovery took some time.

But Santa’s back. Just in time for Christmas.

After surgery, Santa did have radiation because the cancer spread to his lymph nodes. But Dr. Hinni says his future looks bright for many Christmases to come.

December, 2007|Archive|

New report challenges idea that snuff is a safer substitute for cigarettes

  • 12/25/2007
  • Evergreen, VA
  • staff

A 20-year review of scientific research on tobacco and cancer challenges the idea that moist snuff — increasingly popular in the United States — can be a safer substitute for cigarette smoking. The review, by Stephen S. Hecht, is scheduled for the Jan. 1 issue of ACS’ Chemical Research in Toxicology.

The paper, which covers the broad range of research on cancer induced by tobacco, points out that smokeless tobacco, a known cause of oral cancer, is contaminated with levels of cancer-causing nitrosamines that are generally 1,000 times greater than those found in any other consumer product. Despite health warning labels on packages of smokeless tobacco and a ban on electronic advertising, sales of snuff have continued to increase, the paper states.

“In the past several years, a new concept has emerged,” the paper notes. “Responsible members of the tobacco control community support the idea of using ‘low nitrosamine’ moist snuff as a substitute for cigarette smoking. The rationale for this is that moist snuff is demonstrably less carcinogenic in humans, and less toxic in other ways, because it lacks the combustion products.”

However, moist snuff products still contain significant levels of carcinogens, and users should stop, perhaps via use of nicotine replacement therapy, rather than switch from one risky product to another, the paper advises.

December, 2007|Archive|