Up till now, finding out if a mole is a potentially life-threatening melanoma has been a complex task, resulting in both under- and over diagnosis. However, a novel diagnostic staining test has been designed, developed and studied by investigators at Weill Medical College. According to the researchers, the test can provide a new measure of determining whether a mole is benign or cancerous, and has the potential for expanded use across all cancers. The study is published in the Nov. 21 issue of the Archives of Dermatology.
The researchers explain that the novel test, which relies on the soluble adenylyl cyclase (sAC) expression pattern, provides objective results - melanoma is present if sAC is present in the nucleus of cells from a skin biopsy, and benign if the nucleus is not positive.
The majority of diagnostic stains currently used highlight a particular cell in the biopsy. If the stain is more intense it tends to be melanoma, but the definition of 'intense' is subjective.
There are various types of moles, this one is a intradermal nevus
Senior author Dr. Jonathan Zippin, explains:
"The sAC stain is either positive or negative in the cell's nucleus. Other stains require an interpretation of staining intensity, which means that a diagnosis of melanoma can rest on a pathologist's opinion.
As a clinical dermatologist, this uncertainty is difficult to deal with. No one wants to miss a true diagnosis of melanoma, but telling someone they have melanoma, when they may not, changes his or her life."
In order to diagnose melanoma, the skin lesion, together with an area of healthy tissue around it, must be surgically removed, which can result in disfiguration. According to Dr. Zippin, those who are diagnosed with melanoma are concerned they might develop other forms of cancer, as individuals' diagnoses with the disease have a greater risk of developing another cancer.
sAC stain should be used together with other diagnostic tests, such as light microscopy and three other strains currently available, according to the investigation's lead author, Dr. Cynthia Margo.
Dr. Zippin, said:
"What I hope is that five years down the line, this and other stains will help pathologists remove any uncertainty as to whether a biospy is worrisome."
Dr. Margo explains, however, that the sAC provides one benefit that other stains do not. "The greatest practical application of sAC is using it to determine the cancer-free margins of a lentigo maligna that needs to be removed. This is a common melanoma in situ, usually found on the face, that does not show invasive growth. But until the development of sAC, it was very difficult to tell where the cancerous lesion ended." The sAC stain, which Margo uses on several patients, "is vastly superior to any other test we have now to determine margins."
Dr. Zippin explains:
"The new stain is a monoclonal antibody that binds to sAC, which is a signaling molecule," who has studied the molecule. He continues: "sAC senses changes in the interior of cells, such as pH and metabolism, and responds by regulating gene expression, metabolism and growth."
The sAC protein was discovered by Dr. Jochen Buck and Dr. Lonny Levin, both professors of pharmacology at Weill Cornell Medical College.
Dr. Zippin and Dr. Margo developed the antibody used to develop the diagnostic test. As their research gained potential, Dr. Zippin, Dr. Margo, Dr. Buck and Dr. Levin created a company called Cutting Edge Pattern Biotech in order to share the antibody with the scientific community. At present, they are scientific advisers but have no fiscal role in the company.
Dr. Zippin said:
"Beause the sAC protein is expressed in all tissues of the body, and appears to be linked to processes important for the development of cancer, we predict that immunostain will be useful for the diagnosis of many other cancers and diseases."
Even though the diagnostic stain does not require approval from the FDA, the investigators explain that Cutting Edge Pattern Biotech plans to seek federal approval of the sAC antibody as a diagnostic test.
lunedì 5 dicembre 2011
Key To Melanoma Metastasis
Researchers from UNC Lineberger Comprehensive Cancer Center are part of a team that has identified a protein, called P-Rex1, that is key to the movement of cells called melanoblasts. When these cells experience uncontrolled growth, melanoma develops.
Melanoma is one of the only forms of cancer that is still on the rise and is one of the most common forms of cancer in young adults. The incidence of melanoma in women under age 30 has increased more than 50 percent since 1980. Metastases are the major cause of death from melanoma.
The team found that mice lacking the P-Rex1 protein are resistant to melanoma metastases. When researchers tested human melanoma cells and tumor tissue for the protein, P-Rex1 was elevated in the majority of cases - a clue that the protein plays an important role in the cancer's spread. Their findings were published in the journal Nature Communications.
"We know that mutations in a gene called BRAF are important for the development of melanoma and several years ago we published a collaborative paper listing 82 proteins that seem to be affected by this genetic pathway. From that list, we focused on P-Rex1 in collaboration with Dr. Nancy Thomas here at UNC and researchers in the United Kingdom," says Channing Der, PhD, a member of the UNC research team. Der is Kenan Professor of pharmacology at UNC-Chapel Hill and member of UNC Lineberger.
A drug approved this summer, vemurafenib, is the first treatment directed at the BRAF mutation. Clinical trials found that the treatment offers a significant survival benefit.
"We think that vemurafenib may work, in part, by blocking the up-regulation of P-Rex1," Der adds.
"As a physician and scientist, I know firsthand the frustration of having very limited therapeutic options to offer to patients with metastatic melanoma," says Nancy Thomas, MD, PhD, whose laboratory analyzed the protein's expression in human cells. "Pinpointing that P-Rex1 plays a key role in metastasis gives us a better understanding of how vemurafenib may work and a target for developing new treatments," she adds.
Melanoma is one of the only forms of cancer that is still on the rise and is one of the most common forms of cancer in young adults. The incidence of melanoma in women under age 30 has increased more than 50 percent since 1980. Metastases are the major cause of death from melanoma.
The team found that mice lacking the P-Rex1 protein are resistant to melanoma metastases. When researchers tested human melanoma cells and tumor tissue for the protein, P-Rex1 was elevated in the majority of cases - a clue that the protein plays an important role in the cancer's spread. Their findings were published in the journal Nature Communications.
"We know that mutations in a gene called BRAF are important for the development of melanoma and several years ago we published a collaborative paper listing 82 proteins that seem to be affected by this genetic pathway. From that list, we focused on P-Rex1 in collaboration with Dr. Nancy Thomas here at UNC and researchers in the United Kingdom," says Channing Der, PhD, a member of the UNC research team. Der is Kenan Professor of pharmacology at UNC-Chapel Hill and member of UNC Lineberger.
A drug approved this summer, vemurafenib, is the first treatment directed at the BRAF mutation. Clinical trials found that the treatment offers a significant survival benefit.
"We think that vemurafenib may work, in part, by blocking the up-regulation of P-Rex1," Der adds.
"As a physician and scientist, I know firsthand the frustration of having very limited therapeutic options to offer to patients with metastatic melanoma," says Nancy Thomas, MD, PhD, whose laboratory analyzed the protein's expression in human cells. "Pinpointing that P-Rex1 plays a key role in metastasis gives us a better understanding of how vemurafenib may work and a target for developing new treatments," she adds.
Metastatic Breast And Ovarian Cancer Vaccine - Promising Results
A trial published in Clinical Cancer Research demonstrated a positive response in both metastatic breast cancer and ovarian cancer to a recombinant poxviral vaccine.
Lead investigator James Gulley, M.D., Ph.D., director and deputy chief of the clinical trials group at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute commented:
"With this vaccine, we can clearly generate immune responses that lead to clinical responses in some patients."
For the trial, funded by the National Cancer Institute, Gulley and his team involved 26 patients, all of them heavily pretreated, with 21 patients receiving at least three prior chemotherapy treatments, and designated them to receive monthly vaccinations with PANVAC vaccine that contains transgenes for MUC-1, CEA and three T cell costimulatory molecules.
In 12 breast cancer patients the team established an average time to disease progression of 2.5 months and an average overall survival rate of 13.7 months. In four patients the disease was stable. The average time to progression for the 14 ovarian cancer patients was two months and the average survival rate of 15 months.
The most common side effect after treatment was mild reactions at the injection-site.
Because of the rising interest in cancer vaccinations, Gulley recommends for further studies to be conducted in order to establish which vaccines are beneficial for particular patients.
He concludes:
"The sustained benefit seen in some patients in this study underscores the potential for therapeutic vaccines to impact clinical outcomes without toxicity. However, more studies in the appropriate patient populations are required to adequately assess efficacy."
Lead investigator James Gulley, M.D., Ph.D., director and deputy chief of the clinical trials group at the Laboratory of Tumor Immunology and Biology at the National Cancer Institute commented:
"With this vaccine, we can clearly generate immune responses that lead to clinical responses in some patients."
For the trial, funded by the National Cancer Institute, Gulley and his team involved 26 patients, all of them heavily pretreated, with 21 patients receiving at least three prior chemotherapy treatments, and designated them to receive monthly vaccinations with PANVAC vaccine that contains transgenes for MUC-1, CEA and three T cell costimulatory molecules.
In 12 breast cancer patients the team established an average time to disease progression of 2.5 months and an average overall survival rate of 13.7 months. In four patients the disease was stable. The average time to progression for the 14 ovarian cancer patients was two months and the average survival rate of 15 months.
The most common side effect after treatment was mild reactions at the injection-site.
Because of the rising interest in cancer vaccinations, Gulley recommends for further studies to be conducted in order to establish which vaccines are beneficial for particular patients.
He concludes:
"The sustained benefit seen in some patients in this study underscores the potential for therapeutic vaccines to impact clinical outcomes without toxicity. However, more studies in the appropriate patient populations are required to adequately assess efficacy."
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