Platinum-based chemotherapy in metastatic breast cancer : current status

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently ∼60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer. © 2003 Elsevier Ltd. All rights reserved.

Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era. The Oncologist 2010; 15: 390-404

Predictive markers for colorectal cancer:current status and future prospects

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Although there is clear evidence of the benefit of chemotherapy in adjuvant and metastatic settings, its use continues to be suboptimal because of intrinsic or acquired drug resistance. 5-Fluorouracil continues to be the mainstay of CRC therapy, and combinations with newer chemotherapeutic agents such as irinotecan and oxaliplatin have resulted in improved response rates and survival. The role of other agents including cyclooxygenase-2 inhibitors, epidermal growth factor receptor, and farnsyl transferase inhibitors remains to be elucidated. Despite these improvements, many patients undergo chemotherapy without benefit. Increased understanding of the biology of CRC has led to the identification of prognostic markers that may help identify patients who will benefit from chemotherapy. Furthermore, studies have also begun to identify markers that predict whether a tumor will respond to a particular chemotherapy. The ultimate goal of this research is to prospectively identify patients who should receive chemotherapy and, thus, to tailor treatment to the molecular profile of the tumor and patient. Such an approach has the potential to dramatically improve response rates. This review highlights potentially important prognostic and predictive factors in CRC and discusses the potential for their use in the treatment of this disease.

Src inhibitors in lung cancer: current status and future directions

Src tyrosine kinases regulate multiple genetic and signaling pathways involved in the proliferation, survival, angiogenesis, invasion, and migration of various types of cancer cells They are frequently expressed and activated in many cancer types, including lung cancer. Several Src inhibitors, including dasatinib, saracatinib, bosutinib, and KX2-391, are currently being investigated in clinical trials. Preliminary results of the use of single-agent Src inhibitors in unselected patients with lung cancer show that these inhibitors have a favorable safety profile and anticancer activity. Their combination with cytotoxic chemotherapy, other targeted therapy, and radiation therapy is currently being explored. In this review, we summarize the rationale for and the current status of Src inhibitor development and discuss future directions based on emerging preclinical data.

[Lymphadenectomy for bladder cancer: current status and controversies]

Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Current status of knowledge about suicide in people with cancer

Aim: To review the current knowledge about suicide in cancer patients. Method: We searchedspecialized databases using keywords for articles published in the last two decades (1990-2010),and compiled and reviewed them in order to: indicate the prevalence of suicide in cancer patientsworldwide and in Colombia, differentiating the data by sex and age; establish the types of cancerthat are associated with suicide, identify risk factors for committing or considering suicide andpresent the strategies of professional and psychological intervention directed at cancer patientswith suicidal ideation and suicide attempts. The present article is a review of the information on thesubject. Results: We found that: in cancer patients, the suicide rate is two times higher thanin the general population; depression, suicidal ideation and location of cancer are some of therisk factors for suicide, and there is a lack of published guidelines for professional managementof the suicidal patient with cancer. Conclusion: The need to carry out research on the topic ofsuicide in cancer patients was established.

Current status of gene therapy for breast cancer: progress and challenges

Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.

Current status of anti-vascular endothelial growth factor therapy in Europe

Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including age-related macular degeneration (AMD), diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress rapidly, causing legal blindness within months of the second eye becoming affected. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Pegaptanib and ranibizumab are both anti-VEGF therapies licensed for the treatment of neovascular AMD in Europe; however, these drugs are not yet available in Japan. This article reviews the available clinical data on anti-VEGF therapies for the treatment of neovascular AMD in Europe, and considers the future of this exciting therapy.

Mesenchymal stem cells in osteoarthritis therapy : current status of theory, technology, and applications

Osteoarthritis (OA) is a chronic, non-inflammatory type of arthritis, which usually affects the movable and weight bearing joints of the body. It is the most common joint disease in human beings and common in elderly people. Till date, there are no safe and effective diseases modifying OA drugs (DMOADs) to treat the millions of patients suffering from this serious and debilitating disease. However, recent studies provide strong evidence for the use of mesenchymal stem cell (MSC) therapy in curing cartilage related disorders. Due to their natural differentiation properties, MSCs can serve as vehicles for the delivery of effective, targeted treatment to damaged cartilage in OA disease. In vitro, MSCs can readily be tailored with transgenes with anti-catabolic or pro-anabolic effects to create cartilage-friendly therapeutic vehicles. On the other hand, tissue engineering constructs with scaffolds and biomaterials holds promising biological cartilage therapy. Many of these strategies have been validated in a wide range of in vitro and in vivo studies assessing treatment feasibility or efficacy. In this review, we provide an outline of the rationale and status of stem-cell-based treatments for OA cartilage, and we discuss prospects for clinical implementation and the factors crucial for maintaining the drive towards this goal.

Heterogeneous photocatalytic degradation of phenols in wastewater : a review on current status and developments

In recent years, there has been an enormous amount of research and development in the area of heterogeneous photocatalytic water purification process due to its effectiveness in degrading and mineralising the recalcitrant organic compounds as well as the possibility of utilising the solar UV and visible spectrum. One hundred and twenty recently published papers are reviewed and summarised here with the focus being on the photocatalytic oxidation of phenols and their derivatives, predominant in waste water effluent. In this review, the effects of various operating parameters on the photocatalytic degradation of phenols and substituted phenols are presented. Recent findings suggested that different parameters, such as type of photocatalyst and composition, light intensity, initial substrate concentration, amount of catalyst, pH of the reaction medium, ionic components in water, solvent types, oxidising agents/electron acceptors, mode of catalyst application, and calcination temperatures can play an important role on the photocatalytic degradation of phenolic compounds in wastewater. Extensive research has focused on the enhancement of photocatalysis by modification of TiO2 employing metal, non-metal and ion doping. Recent developments in TiO2 photocatalysis for the degradation of various phenols and substituted phenols are also reviewed.

Current Status of Philanthropy in India

The paper makes an attempt to provide an overview of philanthropy in India. On the one hand, it describes, though briefly, the historical growth of philanthropy and on the other hand it provides a contemporary picture as well. It also deals with the legal framework with which philanthropic institutions function in this country. Further, it provides a glimpse of the tax laws vis-à-vis donations (giving) and also discusses the legal status of the philanthropic institutions.

Current status and future prospects for cultured limbal tissue transplants in Australia and New Zealand

Cultured limbal tissue transplants have become widely used over the last decade as a treatment for limbal stem cell deficiency (LSCD). While the number of patients afflicted with LSCD in Australia and New Zealand is considered to be relatively low, the impact of this disease on quality of life is so severe that the potential efficacy of cultured transplants has necessitated investigation. We presently review the basic biology and experimental strategies associated with the use of cultured limbal tissue transplants in Australia and New Zealand. In doing so, we aim to encourage informed discussion on the issues required to advance the use of cultured limbal transplants in Australia and New Zealand. Moreover, we propose that a collaborative network could be established to maintain access to the technology in conjunction with a number of other existing and emerging treatments for eye diseases.

Mineralogy of chondritic porous aggregates : current status

Chondritic porous aggregates (CPA's) belong to an important subset of small particles (usually between 5 and 50 micrometers) collected from the stratosphere by high flying aircraft. These aggregates are approximately chondritic in elemental abundance and are composed of many thousands of small­er, submicrometer particles. CPA particles have been the subject of intensive study during the past few years [1-3] and there is strong evidence that they are a new class of extraterrestrial material not represented in the meteorite collection [3,4]. However, CPA's may be related to carbonaceous chondrites and in fact, both may be part of a continuum of primitive extraterrestrial materials [5]. The importance of CPA's stems from suggestions that they are very primitive solar system material possibly derived from early formed proto­ planets, chondritic parent bodies, or comets [3, 6]. To better understand the origin and evolution of these particles, we have attempted to summarize all of the mineralogical data on identified CPA's published since about 1976.

Report on a workshop to investigate the current status of environmental bio-acoustic monitoring

This workshop was supported by the Australian Centre for Ecological Analysis and Synthesis (ACEAS, http://www.aceas.org.au/), a facility of the Australian Government-funded Terrestrial Ecosystem Research Network (http://www.tern.org.au/), a research infrastructure facility established under the National Collaborative Research Infrastructure Strategy and Education Infrastructure Fund - Super Science Initiative, through the Department of Industry, Innovation, Science, Research and Tertiary Education. Hosted by: Queensland University of Technology, Brisbane, Queensland. (QUT, http://www.qut.edu.au/) Dates: 8-11 May 2012 Report Editors: Prof Stuart Parsons (Uni. Auckland, NZ) and Dr Michael Towsey (QUT). This report is a compilation of notes and discussion summaries contributed by those attending the Workshop. They have been assembled into a logical order by the editors. Another report (with photographs) can be obtained at: http://www.aceas.org.au/index.php?option=com_content&view=article&id=94&Itemid=96