Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an effort to identify factors in primary tumors that would predict liver metastases, we retrospectively reviewed 102 patients with gastric cancer, and their tissue blocks were restained. New staining methods for elastin and endothelium were used to identify intratumoral vessels. Blood vessel invasion, thus detected, was analyzed quantitatively, as well as qualitatively, according to the location of invasion, the size of the involved vessel, and the mode of invasion. The invasion was then compared with the presence of liver metastasis by the chi 2 test, the Mann-Whitney U test, and the Student t test. Discrimination analysis of factors significantly correlated with liver metastasis was performed with linear discrimination function to identify a predictive model for liver metastasis. Significant differences in qualitative frequency of blood vessel invasion (p less than 0.01), the number of lymph node metastases (p less than 0.05), and the depth of tumor invasion (p less than 0.05) were found in those patients in whom liver metastasis developed, as compared with 5-year disease-free survivors. Quantitative analysis of blood vessel invasion revealed eight other factors correlated with liver metastasis; frequency of blood vessel invasion in the 0.01 to 0.1 mm and 0.1 to 1 mm diameter vessels, in the forms of complete, partial tumor thrombi, and vessel wall invasion, in the submucosa and the subserosa, and the number of anatomic stomach layers involved. Application of the discrimination coefficient to these factors allows prediction of liver metastasis with 81.8% sensitivity, 85.3% specificity, and 83.6% accuracy. Liver metastasis can be predicted from the qualitative and quantitative examination of blood vessel invasion within the primary tumor by the use of an elastic fiber stain.
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PMID:Blood vessel invasion in gastric carcinoma. 168 80

During the years 1945-1965 461 women in the city of Turku, Southwestern Finland, were diagnosed as having a biopsy-verified breast cancer. Four-hundred and thirty-nine patients (95%) with complete clinicopathologic data have now been followed up for a mean of 28 years (range from 22 to 42 years) or until death. The survival rate corrected for intercurrent deaths was 44%, 35%, and 34% 10, 20, and 30 years after the diagnosis, respectively. Only 1.2% of all deaths caused by breast cancer occurred more than 20 years after the diagnosis, and therefore about one third of the patients are likely to be cured. Fifty-six (12.8%) patients developed a second primary breast cancer or cancer of other sites. Survival of the patients diagnosed in the 1960s was better than that of the patients diagnosed earlier (p = 0.02), but the relative percentage of prognostically unfavorable poorly differentiated (Gr III) cancers became smaller with time (p = 0.009). Axillary nodal status was the most important independent prognostic factor for the 342 patients with an operable, unilateral, and invasive breast cancer in Cox's multivariate analysis (p less than 0.001), followed by histologic grade, type of tumor margin, the primary tumor size (p less than 0.001), and the extent of tumor necrosis (p = 0.003). Histologic type, mitotic count, nuclear pleomorphism, extent of tubule formation, amount of elastin, and extent of intraductal tumor growth were also significant prognostic factors in a univariate analysis.
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PMID:Prognostic factors and long-term survival in breast cancer in a defined urban population. 224 65

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities. On the other hand, the primary tumor capsule cultures produced little or no collagenase and elastase activities even though they produced type I collagen. The production of proteases by the primary tumor cultures decreased along with time and with an alteration in the morphology of cell populations and/or passage of the cultures. The three clones of tumor cell cultures produced variable amounts of collagenase in response to induction by phorbol myristate acetate, an agent that stimulates maximal collagenase production. In contrast, all three cloned cultures elaborated significant amounts of elastase that degraded insoluble ligamental elastin, and most of the elastase production was increased further in response to induction by phorbol myristate acetate. Each cloned cell population exhibited differences in their production of collagenase and elastase in parallel with their difference in growth kinetics, yet these cells still possess the distinctive properties of the tumor. However, a unit amount of collagenase produced by each of the cloned cultures, with or without induction by phorbol myristate acetate, was less than that of the primary tumor cultures. Results suggest that some cell types or combination of cell types in the heterogeneous cell population of the tumor and/or their products appear to be responsible for the increased production of collagenase and elastase activities and for the invasiveness of a malignant tumor.
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PMID:Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells. 302 19

Cellular regulatory mechanisms normally maintain a delicate balance between cell proliferation, quiescence and death. The imbalance between these functions resulting from molecular intracellular changes is a key factor in tumorigenesis. Tumor cells detaching from the primary tumor possess a propension for invasion and metastasis formation. These tumor cells can attach, migrate, proliferate and grow in host tissue. The surrounding extracellular matrix (ECM) modulates these functions. It is now widely accepted that cell-matrix interactions play an important role in these processes. Most investigators concentrated their attention on the role of integrins in the above processes. There are, however, only scant data on the role of elastin and its receptors in tumor invasion. Nevertheless, experimental evidence indicates that the 67 kDa elastin-laminin receptor (ELR) subunit plays an important role in tumor invasion by mediating essential tumor cell functions leading to metastases. In this review we will concentrate on the putative role of the 67 kDa ELR subunit in tumor invasion.
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PMID:Putative role of 67 kDa elastin-laminin receptor in tumor invasion. 1208 52

Despite significant improvement in modalities for treatment of cancer that led to a longer survival period, the death rate of patients with solid tumors has not changed during the last decades. Emerging studies have identified several physical barriers that limit the therapeutic efficacy of cancer therapeutic agents such as monoclonal antibodies, chemotherapeutic agents, anti-tumor immune cells, and gene therapeutics. Most solid tumors are of epithelial origin and, although malignant cells are de-differentiated, they maintain intercellular junctions, a key feature of epithelial cells, both in the primary tumor as well as in metastatic lesions. Furthermore, nests of malignant epithelial tumor cells are shielded by layers of extracellular matrix (ECM) proteins (e.g., collagen, elastin, fibronectin, laminin) whereby tumor vasculature rarely penetrates into the tumor nests. In this chapter, we will review potential strategies to modulate the ECM and epithelial junctions to enhance the intratumoral diffusion and/or to remove physical masking of target receptors on malignant cells. We will focus on peptides that bind to the junction protein desmoglein 2 and trigger intracellular signaling, resulting in the transient opening of intercellular junctions. Intravenous injection of these junction openers increased the efficacy and safety of therapies with monoclonal antibodies, chemotherapeutics, and T cells in mouse tumor models and was safe in non-human primates. Furthermore, we will summarize approaches to transiently degrade ECM proteins or downregulate their expression. Among these approaches is the intratumoral expression of relaxin or decorin after adenovirus- or stem cell-mediated gene transfer. We will provide examples that relaxin-based approaches increase the anti-tumor efficacy of oncolytic viruses, monoclonal antibodies, and T cells.
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PMID:Strategies to increase drug penetration in solid tumors. 2389 62

Cancer stem cell (CSC) inhibitors are a new category of investigational drugs to treat metastasis. Salinomycin (Sali) is one of most studied CSC inhibitors and has reached clinical tests. Several drug carriers have been developed to improve efficacy of Sali. However, Sali has not been shown to inhibit metastasis from orthotopic tumors, the gold standard for metastasis. To fill this gap, we developed an immune-tolerant, elastin-like polypeptide (iTEP)-based nanoparticle (iTEP-Sali-ABA NP) that released 4-(aminomethyl)benzaldehyde-modified Sali (Sali-ABA) under acidic conditions. We found that the NP increased the area under the curve (AUC) of Sali-ABA by 30-fold and the tumor accumulation by 3.4-fold. Furthermore, no metastasis was detected in any of the mice given the NP. However, all the mice died of primary tumor burdens. To overcome primary tumor growth and improve the overall survival, we applied a combination therapy consisting of the iTEP-Sali-ABA NP and iTEP NP-delivered paclitaxel. This therapy effectively retarded primary tumor growth, and most importantly, improved the overall survival. In conclusion, delivery of Sali-ABA by the NP, alone or in combination with paclitaxel, was more effective than free Sali-ABA in decreasing metastasis and increasing survival. This iTEP-Sali-ABA NP represents a novel and clinically promising therapy to combat metastasis.
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PMID:An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors. 2706 Feb 12

Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under normoxic environments. In current study, we generated 3D breast cancer cell culture platform consists of photocrosslinkable hydrogels and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer cell lines derived from the primary tumor and pleural effusion from the same patient. We demonstrated that hypoxia decreased cellular assembly size and density, and promoted epithelial to mesenchymal transition (EMT) process, without affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell migration, and expression and secretion of lysyl oxidase (LOX), which is copper-dependent amine oxidase and has the primary function to drive the crosslinking of collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in vivo situation, we generated breast cancer and lung cells (derived from the same patient) contact model by stacking 3D hydrogel constructs with breast cancer cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this model for future screen of therapeutic agents, we demonstrated that LOX inhibitor exhibited a significant decrease in breast cancer cell viability, migration, and EMT. Taken together, these results validate the use of hydrogels based models to examine hypoxia related EMT in breast cancer cells.
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PMID:3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition. 3018 9