Current Cancer Therapy Reviews - Volume 10, Issue 1, 2014

Abnormal angiogenesis is a critical feature of many diseases, including cancers and their precursors. Although the association between prostate carcinogenesis and changes in microvascular architecture is well known, these changes are not well-documented from a quantitative point of view. The present study is a review about stereological estimates of the number of quiescent and proliferative endothelial cells, and length of both blood and lymphatic microvessels in normal and prostate cancer tissues. A decrease of endothelial cell density, together with an increase of microvessel length density, was detected in prostate cancer specimens. When comparing blood and lymphatic microvessels the next findings were remarked: The length density from blood vessels was greater than in lymphatics. The average vascular diameter for lymphatics was decreased in cancer in comparison with controls. The endothelial cells per unit of volume were higher in blood vessels than in lymphatics. The surface density of endothelium and the average of endothelial cell surface, were similar in blood and lymphatic vessels in all the groups irrespective of normal, intratumoral or peritumoral locations. The average vascular diameter was the only parameter that in the lymphatics shows a gradient of decreasing from normal to intratumoral tissues, due to mechanical compression by the growing tumour. In contrast with the angiogenesis observed in prostate cancer, the lymphangiogenesis seems to be not relevant. The relevance of the quantification of the blood and lymph microvessels for evaluating anti-angiogenesis strategies in the therapy of prostate cancer is discussed.

Introduction: Increased detection of organ-confined prostate cancer has led to an increased demand for nerve- sparing surgery. Most studies of erectile dysfunction (ED) following nerve-sparing radical prostatectomy (RRP) use single-item assessment and potency rates differ widely among various groups. We aimed to investigate the use of the IIEF-5, a validated questionnaire, for reporting ED following RRP. Aims: To study the use of the IIEF-5 questionnaire in the evaluation of post-RRP ED and to find possible variations in ED reporting when comparing IIEF-5 to single-item assessment. Methods: At a minimum of 18 months post-surgery, patients completed a questionnaire on erectile function that included both single-item assessment and the IIEF-5. The study included sexually active patients who reported no pre-operative ED and who did not receive adjuvant or salvage therapy. Main Outcome Measures: For the single-item assessment, potency was defined as “the ability to achieve erections firm enough for intercourse”. For the IIEF-5 questionnaire, potency was defined as a score > 22 (out of 25) points. Results: Ninety-one patients were included in the study. The procedures consisted of bilateral nerve-sparing (55%) or unilateral or partial bilateral nerve-sparing surgery (45%). We found a striking difference in potency rates when using either IIEF-5 score or single-item assessment for reporting of potency after RRP. The results when using the IIEF-5 questionnaire indicated that 25.5% of all patients were potent. In contrast, single-item assessment indicated a potency rate of 53.8%. Conclusions: Using the IIEF-5 questionnaire to evaluate ED following RRP results in a remarkably lower percentage of men being classified as having no ED. This might be the main reason IIEF-5 is not frequently used in the reporting of ED following radical prostatectomy. Literature search reveals that the IIEF-5 questionnaire is expected to have a higher level of validity, accuracy, and reliability, and may be more stable than single-item assessment. We think that the use of IIEF-5 in the reporting of ED following RRP enhances comparison of different series and of different treatment modalities. However, a prospective comparison between IIEF-5 and single-item assessment is needed to confirm this finding.

Hepatocellular carcinoma is one of the most prevalent forms of cancer throughout the globe. Despite this, therapy of HCC continues to be challenging because of the drawbacks of current treatments options. Lately, nanoparticulate based drug delivery systems have been employed for treatment of variety of cancers, including primary hepatic cancer. These nanocarriers can be tailored to meet the desired requirements on the basis of their size, charge, composition and surface properties. Following attachment to a targeting ligand, the deleterious and toxic effects associated with the drug could be reduced to a minimum, along with site selective delivery of antineoplastic agents. This article attempts to present a review of various nanoparticulate delivery systems which have been explored for the remedy of hepatocellular carcinoma.

The mitogen-activated protein kinase (MAPK) signaling pathway plays a fundamental role in the carcinogenesis of colorectal and numerous other neoplasms. The development of targeted agents that inhibit MEK 1 and 2 has created the potential for downstream blockade of the MAPK pathway. Though MEK inhibition has demonstrated clinically significant efficacy in several tumor types, therapeutic success has been limited in colorectal cancer (CRC). This review will describe the current experience with MEK inhibition. It will also highlight ongoing efforts and future directions, including potential rational combination strategies and the investigation into potential predictive biomarkers of response.

Small cell lung cancer (SCLC) is a rapidly progressive malignancy with no improvement in survival outcome or change in the standard of care over the past thirty years. In this review, we examine molecular tissue markers, serum/ plasma markers, laboratory data and clinical markers that have been reported to have prognostic influence in SCLC. We discovered that the following held a poor prognosis in limited (LD) and extensive-stage (ED) SCLC: Autocrine growth loop activity via C-kit, gastrin-releasing peptide, or pro-gastrin releasing peptide, high pre-treatment beta fibroblast growth factor, increased cathepsin B or D expression, reduced intracellular fragile histidine triad protein expression, her-2/neu over-expression, high matrix metalloproteinase-11 or -14 activity, loss of function of Rb, elevated serum levels of ALT, CEA, CRP, LDH, or VEGF, hyponatremia, elevated lymphatic/vascular endothelial progenitor, disease extent, male gender, weight loss, anemia, neutrophilia, thrombocytopenia, prolonged PT or aPTT, and superior vena cava syndrome as part of an initial presentation of disease. Hypourecemia, elevated neuron-specific enolase, and age over 70 years conveyed a poorer prognosis in LD and elevated creatinine, higher performance status (> 2), and liver, bone, or brain metastases conveyed a poorer prognosis in ED SCLC. The following conveyed a favorable prognosis in LD and ED SCLC: E-cadherin expression, increased cytoplasmic levels of inhibitor of DNA binding/differentiation-2, increased numbers of tumor-infiltrating lymphocytes, high MAPK activity, normal to elevated albumin levels, female gender, performance status <2, and smoking cessation at time of diagnosis. Age <70 and the absence of a pleural effusion were associated with a better prognosis in LD only. The data supporting many of these prognostic factors are somewhat weak and reflect that lack of translational research in this disease.

Systemic anticancer therapies may produce several toxicities including eye adverse events. In fact, contrary to general belief, the eye is a really sensitive organ. These adverse events may vary between a simple lacrimation to a marked irreversible visual loss even at therapeutic doses. A review of the literature was conducted showing that ocular toxicity is not as uncommon as previously thought and unfortunately in most cases, the mechanism underlying this continue to be poorly understood. Dealing with this toxicity is relevant and a close collaboration between oncologists, ophthalmologists and pharmacists would be advisable to reduce the incidence of serious toxicities.

Tumors are complex tissues composed of different cell types that interact with one another by building up complicated intra-and intercellular signal networks. In addition to the proliferating cancer cells, tumors also contain normal cells which are recruited and eroded by cancer cells to form tumor-supportive stroma and these natively normal stromal cells actively participate in the tumor development and progression by editing some of the behaviors of cancer cells and creating a tumor microenvironment to foster the rapid growth and proliferation of cancer cells. Therefore, the genetically mutated cancer cells are the cell of origin and driving forces for tumor development and progression. Selectively targeting cancer cells to induce tumor cell death and intercepting or normalizing the interaction signal network between the cancer and stromal cells are the bases for current cancer therapies. Identification of the mutated components in the intrinsic and extrinsic apoptotic pathways in cancer cells and designing small molecule mimetics or agonists to eradicate cancer cells by selectively targeting these mutations represent the attractive strategies for modern cancer therapy.

Introduction: The UK government introduced the two-week rule (TWR) to improve the diagnosis and treatment of gastrointestinal (GI) cancers. This updated review systematically identifies new articles since 2009 and presents an overview of the previous and new findings combined for both upper GI cancer (UGCs) and colorectal cancers (CRCs). Methods: We analysed all peer-reviewed articles and conference abstracts with GI cancer detection rates following TWR referral and/or the proportion of TWR-referred GI cancers from the total number diagnosed during the study period. We reported average cancer detection rates and split the data according to four time periods to determine whether TWR effectiveness improved over time. Results: The average cancer detection rate by the TWR for all studies was 11.6% for CRC and 8.3% for UGC. We found a decrease in cancer detection rates over time for CRC from 14.4% in 2000-2002 to 7.2% in 2009-2012. However, UGC detection rates increased over time from 8.5% in 2000-2002 to 11.4% in 2005-2008. We found that on average, 30.8% of CRCs and 28.8% of UGCs were detected following referrals using the TWR system and that these proportions had increased over time from 30.6% to 38.4% for CRC and from 26.8% to 52% for UGC. Conclusion: The TWR is not still sufficiently effective in diagnosing GI cancers in patients, suggesting that the referral guidelines need to be improved. Our findings do suggest that the TWR is being used more frequently than alternative routes.