Melanoma, a malignant tumor of melanocytes, is the most serious type of skin cancer in the world. It accounts for about 80% of deaths of all skin cancer. For cancer detection, circulating tumor cells (CTCs) serve as a marker for metastasis development, cancer recurrence, and therapeutic efficacy. Melanoma tumor cells have high content of melanin, which has high light absorption and can serve as endogenous biomarker for CTC detection without labeling. Here, we have developed an in vivo photoacoustic flow cytometry (PAFC) to monitor the metastatic process of melanoma cancer by counting CTCs of melanoma tumor bearing mice in vivo. To test in vivo PAFC’s capability of detecting melanoma cancer, we have constructed a melanoma tumor model by subcutaneous inoculation of highly metastatic murine melanoma cancer cells, B16F10. In order to effectively distinguish the targeting PA signals from background noise, we have used the algorithm of Wavelet denoising method to reduce the background noise. The in vivo flow cytometry (IVFC) has shown a great potential for detecting circulating tumor cells quantitatively in the blood stream. Compared with fluorescence-based in vivo flow cytometry (IVFC), PAFC technique can be used for in vivo, label-free, and noninvasive detection of circulating tumor cells (CTCs).
Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every
year. Hepatocellular carcinoma may metastasize to lung, bones, kidney, and many other organs. Surgical resection, liver
transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes
are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to
be understood better and new therapies must be developed. A recently developed "in vivo flow cytometer" combined
with real-time confocal fluorescence imaging are used to assess spreading and the circulation kinetics of liver tumor
cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow
characteristics of fluorescently labeled cells in vivo in real time without extracting blood sample. We have measured the
depletion kinetics of two related human HCC cell lines, high-metastatic HCCLM3 cells and low-metastatic HepG2 cells,
which were from the same origin and obtained by repetitive screenings in mice. >60% HCCLM3 cells are depleted
within the first hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In
comparison, <40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide
insights into early metastasis processes.
Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer,
after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time,
the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize
throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy,
chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause
both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer
metastasis need to be understood better and new therapies must be developed to selectively target to unique
characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the
mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared
fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess
prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of
circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential
therapeutic interventions.
Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer,
after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. During this time,
the tumor produces little or no symptoms or outward signs. As the cancer advances, however, it can metastasize
throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy,
chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause
both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer
metastasis need to be understood better and new therapies must be developed to selectively target to unique
characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the
mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal nearinfrared
fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess
prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. A real- time quantitative monitoring of
circulating prostate cancer cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential
therapeutic interventions.
A fiber confocal backscattering (FCBS) spectrometer is developed based on fiber confocal microscopy and light scattering theory. The FCBS spectrometer can provide imaging and spectral information simultaneously at the cellular scale. Normal stomach epithelial cell line GES-1 and cancerous cell line NCI-N87 are measured and their spectral results show that backscattering intensity from NCI-N87 cells is stronger than that from GES-1 cells in 500 to 800 nm, and the GES-1 cells scattering spectra show regular intensity changes, while the NCI-N87 cells do not. The experiments prove that the FCBS spectrometer is able to distinguish cancerous cells from normal stomach cells at the cellular level. The spectrometer could be further developed into a noninvasive optical technology for early cancer detection.
A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the
circulation kinetics of liver tumor cells. The in vivo flow cytometer has the capability to detect and quantify the number
and flow characteristics of fluorescently labeled cells in vivo continuously. The depletion rate of circulating tumor cells
provides insights in early cancer metastasis. It is useful to understand the molecular mechanisms of liver tumor
metastasis. A real-time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will help
assess the effectiveness of the potential therapeutic interventions.
Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every
year. This ranges from 15,000 cases in the United States to more than a 250,000 in China. About 80% of people with
primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help,
one third of the patients have cancer that has not progressed beyond the liver. Primary liver cancer (hepatocellular
carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. HCC may metastasize to the lung, bones,
kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the
foundation of current HCC therapies. However the outcomes are
poor-the survival rate is almost zero for metastatic
HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be
developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in
vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo in
real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical
imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real-time
quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the
effectiveness of the potential therapeutic interventions.
Chemotherapies currently constitute one main venue of cancer treatment. For a large number of adult and elderly
patients, however, treatment options are poor. These patients may suffer from disease that is resistant to conventional
chemotherapy or may not be candidates for curative therapies because of advanced age or poor medical conditions. To
control disease in these patients, new therapies must be developed that are selectively targeted to unique characteristics
of tumor cell growth and metastasis. A reliable early evaluation and prediction of response to the chemotherapy is
critical to its success. Chemotherapies induce apoptosis in tumor cells and a portion of such apoptotic cancer cells may
be present in the circulation. However, the fate of circulating tumor cells is difficult to assess with conventional methods
that require blood sampling. We report the in situ measurement of circulating apoptotic cells in live animals using in
vivo flow cytometry, a novel method that enables real-time detection and quantification of circulating cells without blood
extraction. Apoptotic cells are rapidly cleared from the circulation with a half-life of ~10 minutes. Real-time monitoring
of circulating apoptotic cells can be useful for detecting early changes in disease processes, as well as for monitoring
response to therapeutic intervention.
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