Breast Cancer, Chemokines, And Metastasis: A Search for Decoy Ligands of the CXCR4 Receptor

Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates.

Statins and Lung Cancer: A Review of Current Literature

Cardiovascular disease and lung cancer are two of the most common causes of death in the United States. The cardioprotective benefits of statin class drugs is predominantly mediated through the inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, decreasing available mevalonate, and thus limiting in vivo cholesterol biosynthesis. Mevalonate and its metabolites have significant roles in cellular membrane synthesis, which is dysregulated during tumorigenesis, and is therefore a potential source for anti-tumor effects of statins. Similarly, dysregulation of cellular signaling is a hallmark of tumorigenesis. In vitro studies of EGFR, RAS, and AKT signaling pathways in cancer cells can all be reformed back to states more indicative of normally functioning cells when treated with statins. Statins have also been shown to exert beneficial properties in the presence of chemotherapeutic medications and radiation therapies by modulating the deleterious effects of reactive oxygen species, decreasing tumor cell resistance, and minimizing damage to surrounding native tissues. There is abundant of in vitro evidence to support the beneficial effects of statins on lung cancer patients. Prospective studies to determine the value of statin therapy on lung cancer prevention could lead to a significant change in lung cancer treatment.

Rare Lipomatous Neoplasm of The Thigh in A 13 Year Old Male with A Discussion of Imaging Features and Differential Diagnosis of A Fatty Extremity Mass

Lipomatous tumors are among the most common primary musculoskeletal neoplasms affecting both pediatric and adult patient populations. Patient age, tumor location, and imaging features all contribute to the differential diagnosis of musculoskeletal tumors. Tumors identified outside of common patient demographics or in unusual locations may lead to preoperative misdiagnosis. We present an uncommon adipocytic tumor occurring at an uncommon age which was proven at surgery to represent a preoperatively unexpected diagnosis. A 13 year old male presented with a fatty anterior proximal thigh mass; age and magnetic resonance findings suggested lipoblastoma. However, following complete surgical resection, histopathology confirmed hibernoma, a benign lipomatous tumor characterized by the presence of white and multivacuolated brown fat cells, the vast majority of which occur in adult patients.

Tumor Growth Dynamics: Dietary Fish Oil Induced Inhibition of Human Breast Carcinoma Growth, A Phenomenon of Reduced Cellular DNA Synthesis or Increased Cell Loss?

Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.

The Role of Heparin in Lung Cancer

Non-small cell lung cancer is a major health problem worldwide. Surgery is still the mainstay of treatment especially in early stages of the disease. Despite the fact that surgery is the potentially curative treatment, the recurrence and mortality rates are still high specifically with more advanced stages of cancer. Heparin has been suggested to have a positive impact on the outcome of various cancers through its anticoagulants properties and; in some instances; due to their antitumor activity. Recently, the molecular mechanisms of tumor cell spreading have been recognised. Metastasis is a complex process that could be therapeutically affected wherever certain extra-cellular matrix proteins could play an important role in prevention of tumor cell migration and invasion. Experimental studies have shown decreased metastases development after heparin use in rat models. We have reviewed the literature to study the role of anticoagulants in cancer patients in general and in patients with Non Small Cell Lung Cancer (NSCLC) specifically.