A mini-symposium was held in Montreal, Canada, at the International Surgical Week for the Breast Surgical International in 2007 addressing the question whether breast cancer is the same disease in ...Asian and Western countries. Numerous investigators from Asian and Western countries presented the epidemiologic and clinical outcome data of women with breast cancer. Although there are significant similarities, the striking difference is that the peak age for breast cancer is between 40 and 50 years in the Asian countries, whereas the peak age in the Western countries is between 60 and 70 years. Also, the incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is increasing, the mortality rate is definitely decreasing. Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries.
Background
Whether breast cancer is the same disease in Asian and Western countries was the topic of a 2007 Breast Surgery International symposium at International Surgical Week.
Methods
Participating investigators from China, Taiwan, India, Japan, South Korea, Sweden, Canada, and the United States were asked beforehand to provide data on the epidemiology and treatment outcome of women in their countries.
Results
Comparisons of the epidemiologic and clinical outcome data of women with breast cancer showed significant similarities, but the striking difference is that the peak age is between 40 and 50 years in Asian countries, but is between 60 and 70 years in Western countries. The incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is also increasing, the mortality rate is definitely decreasing.
Discussion
Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries.
Technetium-99m-labeled Tilmanocept or Lymphoseek® (Cardinal Health, Dublin, Ohio) is a soluble, synthetic molecule with a small diameter (7 nm), which is comprised of technetium-99m chelated to a ...dextran backbone containing multiple units of mannose ligands with a high affinity for CD206, a receptor located on the surface of macrophages and dendritic cells that are found in high concentration in lymph nodes. It enables quick transit from the injection site and rapid lymph node accumulation. The binding of mannose ligand and CD206 results in the internalization of the ligand and receptor into the cell. Once the Technetium-99m-labeled Tilmanocept (Lymphoseek®) reaches the lymph node, it is readily internalized by the macrophages and dendritic cells within the draining lymph nodes. Technetium-99m-labeled Tilmanocept (Lymphoseek®) has been extensively studied as a radioisotope for detection of sentinel lymph nodes in melanoma, breast cancer and head and neck squamous cell carcinoma in clinical trials. Based on its safety and ability to detect sentinel lymph nodes satisfactorily, it has been approved by the FDA to use as a radioisotope for preoperative lymphoscintigraphy for identification of sentinel lymph nodes in these types of cancer. Further, the FDA has expanded approval of Technetium-99m-labeled for sentinel lymph node mapping of all solid tumors as well as in pediatric patients.
Cancer metastasis is the process by which primary cancer cells invade through the lymphatic or blood vessels to distant sites. The molecular mechanisms by which cancer cells spread either through the ...lymphatic versus blood vessels or both are not well established. Two major developments have helped us to understand the process more clearly. First, the development of the sentinel lymph node (SLN) concept which is well established in melanoma and breast cancer. The SLN is the first lymph node in the draining nodal basin to receive cancer cells. Patients with a negative SLN biopsy show a significantly lower incidence of distant metastasis, suggesting that the SLN may be the major gateway for cancer metastasis in these cancer types. Second, the discovery and characterization of several biomarkers including VEGF-C, LYVE-1, Podoplanin and Prox-1 have opened new vistas in the understanding of the induction of lymphangiogenesis by cancer cells. Cancer cells must complete multiple steps to invade the lymphatic system, some of which may be enabled by the evolution of new traits during cancer progression. Thus, cancer cells may spread initially through the main gateway of the SLN, from which evolving cancer clones can invade the blood vessels to distant sites. Cancer cells may also enter the blood vessels directly, bypassing the SLN to establish distant metastases. Future studies need to pinpoint the molecules that are used by cancer cells at different stages of metastasis via different routes so that specific therapies can be targeted against these molecules, with the goal of stopping or preventing cancer metastasis.
Abstract Whether cancer cells metastasize from the primary site to the distant sites via the lymphatic vessels or the blood vessels directly into the circulation is still under intense study. In this ...review article, we follow the journey of cancer cells metastasizing to the sentinel lymph nodes and beyond to the distant sites. We emphasize cancer heterogeneity and microenvironment as major determinants of cancer metastasis. Multiple molecules have been found to be associated with the complicated process of metastasis. Based on the large sentinel lymph node data, it is reasonable to conclude that cancer cells may metastasize through the blood vessels in some cases but in most cases, they use the sentinel lymph nodes as the major gateway to enter the circulation to distant sites.
The Gene Expression Signatures of Melanoma Progression Haqq, Christopher; Nosrati, Mehdi; Sudilovsky, Daniel ...
Proceedings of the National Academy of Sciences - PNAS,
04/2005, Letnik:
102, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma ...progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.
Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the ...oncogenic effects of BPTF in melanoma.
The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines. Immunoblotting was used to assess the expression of various proteins regulated by BPTF. The functional role of BPTF in melanoma progression was investigated using assays of colony formation, invasion, cell cycle, sensitivity to selective BRAF inhibitors, and in xenograft models of melanoma progression (n = 12 mice per group). The biomarker role of BPTF in melanoma progression was assessed using fluorescence in situ hybridization and immunohistochemical analyses. All statistical tests were two-sided.
shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF copy number (mean ≥ 3) was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival P = .03, and disease-specific survival P = .008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell subclones, indicating the continued presence of drug-responsive subclones within tumors demonstrating overall resistance to anti-BRAF agents.
These studies demonstrate multiple protumorigenic functions for BPTF and identify it as a novel target for anticancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF.
Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the ...growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand the cancer microenvironment and host response to cancer growth. Melanoma is an excellent model to study the interaction of cancer initiation and growth in relationship to its microenvironment. Social evolution with cooperative cellular groups within an organism is what gives rise to multicellularity in the first place. Cancer cells evolve to exploit their cellular environment. The foundations of multicellular cooperation break down in cancer because those cells that misbehave have an evolutionary advantage over their normally behaving neighbors. It is important to classify evolutionary and ecological aspects of cancer growth, thus, data for cancer growth and outcomes need to be collected to define these parameters so that accurate predictions of how cancer cells may proliferate and metastasize can be developed.
Background
99m
TcTilmanocept is a CD206 receptor-targeted radiopharmaceutical designed for sentinel lymph node (SLN) identification. Two nearly identical nonrandomized phase III trials compared
99m
...Tctilmanocept to vital blue dye.
Methods
Patients received
99m
Tctilmanocept and blue dye. SLNs identified intraoperatively as radioactive and/or blue were excised and histologically examined. The primary end point, concordance, was the proportion of blue nodes detected by
99m
Tctilmanocept; 90 % concordance was the prespecified minimum concordance level. Reverse concordance, the proportion of radioactive nodes detected by blue dye, was also calculated. The prospective statistical plan combined the data from both trials.
Results
Fifteen centers contributed 154 melanoma patients who were injected with both agents and were intraoperatively evaluated. Intraoperatively, 232 of 235 blue nodes were detected by
99m
Tctilmanocept, for 98.7 % concordance (
p
< 0.001).
99m
TcTilmanocept detected 364 nodes, for 63.7 % reverse concordance (232 of 364 nodes).
99m
TcTilmanocept detected at least one node in more patients (
n
= 150) than blue dye (
n
= 138,
p
= 0.002). In 135 of 138 patients with at least one blue node, all blue nodes were radioactive. Melanoma was identified in the SLNs of 22.1 % of patients; all 45 melanoma-positive SLNs were detected by
99m
Tctilmanocept, whereas blue dye detected only 36 (80 %) of 45 (
p
= 0.004). No positive SLNs were detected exclusively by blue dye. Four of 34 node-positive patients were identified only by
99m
Tctilmanocept, so 4 (2.6 %) of 154 patients were correctly staged only by
99m
Tctilmanocept. No serious adverse events were attributed to
99m
Tctilmanocept.
Conclusions
99m
TcTilmanocept met the prespecified concordance primary end point, identifying 98.7 % of blue nodes. It identified more SLNs in more patients, and identified more melanoma-containing nodes than blue dye.
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