Fruit and vegetable consumption and the risk of proximal colon, distal colon and rectal cancers in a case-control study in Western Australia

Background Fruits and vegetables (F/V) have been examined extensively in nutrition research in relation to colorectal cancer (CRC). However, their protective effect is subject to debate, possibly because of different effects on different subsites of the large bowel.

Objective To determine whether any association between F/V consumption and risk of CRC differed by subsite of the bowel (proximal colon, distal colon, and rectum).

Design The Western Australian Bowel Health Study is a population-based, case-control study conducted between June 2005 and August 2007. Complete food frequency questionnaire data were analysed from 834 CRC cases and 939 controls. Logistic regression analysis was used to estimate the effects of quartiles of F/V intake on risk of CRC at different subsites. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for CRC overall and for the three separate subsites.

Results Risk of proximal colon cancer and rectal cancer was not associated with intakes of total F/V, total vegetable, or total fruit. Brassica vegetable intake was inversely related with proximal colon cancer (Q4 vs Q1 OR 0.62; 95% CI 0.41 to 0.93). For distal colon cancer, significant negative trends were seen for total F/V, and total vegetable intake. Distal colon cancer risk was significantly decreased for intake of dark yellow vegetables (Q4 vs Q1 OR 0.61; 95% CI 0.41 to 0.92) and apples (Q4 vs Q1 OR 0.51; 95% CI 0.34 to 0.77). An increased risk for CRC was found to be associated with intake of fruit juice (Q4 vs Q1 OR 1.74; 95% CI 1.24 to 2.45).

Conclusions Our results suggest that different F/V may confer different risks for cancer of the proximal colon, distal colon, or rectum. Future studies might consider taking into account the location of the tumor when examining the relation between F/V consumption and risk of CRC.

Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

The recurrence and metastatic spread of cancer are major drawbacks in cancer treatment. Although chemotherapy is one of the most effective methods for the treatment of metastatic cancers, it is nonspecific and causes significant toxic damage. The development of drug resistance to chemotherapeutic agents through various mechanisms also limits their therapeutic potential. However, as we discuss here, the use of nanodelivery systems that are a combination of diagnostics and therapeutics (theranostics) is as relatively novel concept in the treatment of cancer. Such systems are likely to improve the therapeutic benefits of encapsulated drugs and can transit to the desired site, maintaining their pharmaceutical properties. The specific targeting of malignant cells using multifunctional nanoparticles exploits theranostics as an improved agent for delivering anticancer drugs and as a new solution for overriding drug resistance.

Clinical aspects for survivin: a crucial molecule for targeting drug-resistant cancers

Drug resistance is frequently found in cancer patients who have prolonged chemotherapeutic treatments. Overcoming this phenomenon to make therapy available to these patients is one of the most important features in developing effective cancer therapeutic strategies. Identification of drug resistance causative molecules is one of the most focused areas of cancer research today. Many molecules have been identified in conferring cancer cells the property of drug resistance, and various small molecule inhibitors have been developed to target these molecules to restore the sensitivity of different traditional chemotherapeutic agents, which are frequently found to exhibit reduced potency during prolonged treatment, in cancer patients. Survivin, a member of the inhibitor of apoptosis proteins (IAP) family, has been identified as one of the most crucial biomarkers in the recognition of drug resistance. Survivin is overexpressed in tumor cells, helping in its proliferation and survival, and its overexpression is positively correlated with poor prognosis for cancer patients. Targeted therapeutic measures to inhibit survivin in cancers, particularly drug-resistant tumors, are the recent focus of research for cancer treatment.

Accepting risk in the acceleration of drug development for rare cancers.

Rare cancers collectively contribute a disproportionate fraction of the total burden of cancer. The oncology community is increasingly facing small numbers of patients with each cancer subtype, requiring cooperation and collaboration to complete multicentre trials that advance knowledge and patient care. At the same time, new insights into the biology of rare cancers have led to an explosion in knowledge and development of targeted agents. These insights and techniques are set to revolutionise the care of patients with cancer. However, drug development strategies and the availability of new agents for rare cancers are at risk of stalling owing to the ever-increasing complexity and costs of clinical trials. Finding solutions to these problems is imperative to the future of cancer care. We propose that a greater degree of risk sharing is needed than is currently accepted to enable the use of new methods with confidence, and to keep pace with scientific advancement.

Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers

The present study successfully developed orally deliverable multimodular zinc (Zn) iron oxide (Fe3O4)-saturated bovine lactoferrin (bLf)-loaded polymeric nanocapsules (NCs), and evaluated their theranostic potential (antitumor efficacy, magnetophotothermal efficacy and imaging capability) in an in vivo human xenograft CpG-island methylator phenotype (CIMP)-1(+)/CIMP2(-)/chromosome instability-positive colonic adenocarcinoma (Caco2) and claudin-low, triple-negative (ER(-)/PR(-)/HER2(-); MDA-MB-231) breast cancer model. Mice fed orally on the Zn-Fe-bLf NC diet showed downregulation in tumor volume and complete regression in tumor volume after 45 days of feeding. In human xenograft colon cancer, vehicle-control NC diet-group (n=5) mice showed a tumor volume of 52.28±11.55 mm(3), and Zn-Fe-bLf NC diet (n=5)-treated mice had a tumor-volume of 0.10±0.073 mm(3). In the human xenograft breast cancer model, Zn-Fe-bLf NC diet (n=5)-treated mice showed a tumor volume of 0.051±0.062 mm(3) within 40 days of feeding. Live mouse imaging conducted by near-infrared fluorescence imaging of Zn-Fe-bLf NCs showed tumor site-specific localization and regression of colon and breast tumor volume. Ex vivo fluorescence-imaging analysis of the vital organs of mice exhibited sparse localization patterns of Zn-Fe-bLf NCs and also confirmed tumor-specific selective localization patterns of Zn-Fe-bLf NCs. Dual imaging using magnetic resonance imaging and computerized tomography scans revealed an unprecedented theranostic ability of the Zn-Fe-bLf NCs. These observations warrant consideration of multimodular Zn-Fe-bLf NCs for real-time cancer imaging and simultaneous cancer-targeted therapy.

Transmissible cancers in an evolutionary context.

Cancer is an evolutionary and ecological process in which complex interactions between tumour cells and their environment share many similarities with organismal evolution. Tumour cells with highest adaptive potential have a selective advantage over less fit cells. Naturally occurring transmissible cancers provide an ideal model system for investigating the evolutionary arms race between cancer cells and their surrounding micro-environment and macro-environment. However, the evolutionary landscapes in which contagious cancers reside have not been subjected to comprehensive investigation. Here, we provide a multifocal analysis of transmissible tumour progression and discuss the selection forces that shape it. We demonstrate that transmissible cancers adapt to both their micro-environment and macro-environment, and evolutionary theories applied to organisms are also relevant to these unique diseases. The three naturally occurring transmissible cancers, canine transmissible venereal tumour (CTVT) and Tasmanian devil facial tumour disease (DFTD) and the recently discovered clam leukaemia, exhibit different evolutionary phases: (i) CTVT, the oldest naturally occurring cell line is remarkably stable; (ii) DFTD exhibits the signs of stepwise cancer evolution; and (iii) clam leukaemia shows genetic instability. While all three contagious cancers carry the signature of ongoing and fairly recent adaptations to selective forces, CTVT appears to have reached an evolutionary stalemate with its host, while DFTD and the clam leukaemia appear to be still at a more dynamic phase of their evolution. Parallel investigation of contagious cancer genomes and transcriptomes and of their micro-environment and macro-environment could shed light on the selective forces shaping tumour development at different time points: during the progressive phase and at the endpoint. A greater understanding of transmissible cancers from an evolutionary ecology perspective will provide novel avenues for the prevention and treatment of both contagious and non-communicable cancers.