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Nanocarriers for nuclear imaging and radiotherapy of cancer.

Several nanoscale carriers (nanoparticles, liposomes, water-soluble polymers, micelles and dendrimers) have been developed for targeted delivery of cancer diagnostic and therapeutic agents. These carriers can selectively target cancer sites and carry large payloads, thereby improving cancer detection and therapy effectiveness. Further, the combination of newer nuclear imaging techniques providing high sensitivity and spatial resolution such as dual modality imaging with positron emission tomography/computed tomography (PET/CT) and use of nanoscale devices to carry diagnostic and therapeutic radionuclides with high target specificity can enable more accurate detection, staging and therapy planning of cancer. The successful clinical applications of radiolabeled monoclonal antibodies for cancer detection and therapy bode well for the future of nanoscale carrier systems in clinical oncology. Several radiolabeled multifunctional nanocarriers have been effective in detecting and treating cancer in animal models. Nonetheless, further preclinical, clinical and long-term toxicity studies will be required to translate this technology to the care of patients with cancer. The objective of this review is to present a brief but comprehensive overview of the various nuclear imaging techniques and the use of nanocarriers to deliver radionuclides for the diagnosis and therapy of cancer.

Animals↗

REporting recommendations for tumour MARKer prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. Similar to the successful CONSORT initiative for randomised trials and the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

Reporting recommendations for tumor marker prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

Reporting recommendations for tumor marker prognostic studies (remark).

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute - European Organisation for Research and Treatment of Cancer (NCI - EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

REporting recommendations for tumor MARKer prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

REporting recommendations for tumour MARKer prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomised trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

REporting recommendations for tumor MARKer prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons why multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines provide helpful suggestions on how to present data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

REporting recommendations for tumor MARKer prognostic studies (REMARK).

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons why multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostic in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines provide helpful suggestions on how to present data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

Biomarkers, Tumor↗

Protein expression profiling identifies macrophage migration inhibitory factor and cyclophilin a as potential molecular targets in non-small cell lung cancer.

Current diagnostic and therapeutic strategies for lung cancer have had no significant impact on lung cancer mortality over the last several decades. This study used a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) discovery platform to generate protein expression profiles in search of overexpressed proteins in lung tumors as potentially novel molecular targets. Two differentially expressed protein peaks at m/z 12338 and 17882 in the MALDI-TOF spectra were identified in lung tumor specimens as macrophage migration inhibitory factor and cyclophilin A, respectively. Overexpression of both proteins was confirmed by Western blotting, and cyclophilin A was localized to the tumor cells by immunohistochemistry. These data demonstrate the feasibility of using a MALDI-TOF platform to generate protein expression profiles and identify potential molecular targets for cancer diagnostics and therapeutics.

Amino Acid Sequence↗

Mass spectrometry: uncovering the cancer proteome for diagnostics.

Despite impressive scientific achievements over the past few decades, cancer is still a leading cause of death. One of the major reasons is that most cancer patients are diagnosed with advanced disease. This is clearly illustrated with ovarian cancer in which the overall 5-year survival rates are only 20-30%. Conversely, when ovarian cancer is detected early (stage 1), the 5-year survival rate increases to 95%. Biomarkers, as tools for preclinical detection of cancer, have the potential to revolutionize the field of clinical diagnostics. The emerging field of clinical proteomics has found applications across a wide spectrum of cancer research. This chapter will focus on mass spectrometry as a proteomic technology implemented in three areas of cancer: diagnostics, tissue imaging, and biomarker discovery. Despite its power, it is also important to realize the preanalytical, analytical, and postanalytical limitations currently associated with this methodology. The ultimate endpoint of clinical proteomics is individualized therapy. It is essential that research groups, the industry, and physicians collaborate to conduct large prospective, multicenter clinical trials to validate and standardize this technology, for it to have real clinical impact.

Animals↗

[Risk estimation for thyroid cancer induced by diagnostic radiation doses (authors transl)].

Cancer of the thyroid has been detected as a late consequence of irradiation mainly for benign diseases. A survey of data from several investigators shows a strong correlation between incidence and thyroid dose. The result of a risk estimation for irradiated children assuming a linear non-threshold dose response is 60 cancers per 10(6) per rem in 20 years following irradiation. There is no evidence that adults will be much less sensitive. Radiation risks for the thyroid should be considered in nuclear medicine, because the diagnostic use of radioiodine leads to organ doses which are comparably high.

Humans↗

Identifying biomarkers and surrogates of tumors (cancer biometrics): correlation with immunotherapies and immune cells.

The presence of inflammatory cells within cancer has been described for quite some time by pathologists, with generally improved outcome associated with their presence in various epithelial neoplasms. Most remarkably, this has included dendritic cells and T cells but more recently NK cells as well. Coupled with the rapid evolution of molecular technology, microarray analyses of primary tumors, serum and tumor proteomics, tumor capture analyses in the peripheral blood (together with quantitative RT-PCR), and novel histochemical markers and tissue microarrays, this provides the opportunity to establish a more effective means to study and classify into subsets various forms of cancer. Much of the current controversy in cancer diagnosis and pathologic assessment of prognosis lies in the application of these techniques in concert with other molecular tools including DNA microarrays, expression of histochemically defined cytokines, proangiogenic factors, and oncogene products, and correlating this with clinical relevance. Molecular detection technologies such as reverse transcriptase polymerase chain reaction, proteomics, and microarray analyses will be validated based on their integration with conventional cancer pathology and cancer diagnostics. Further work is needed to establish which cancer biomarkers and surrogates should be routinely measured and in which settings, and determining the appropriate sample size for such assays that can be validated in retrospective and prospective clinical studies. The ability to integrate these rapidly evolving strategies will consume much of our coordinate effort in cancer and cancer therapeutics for the near future.

Biomarkers, Tumor↗

[Relation of breast cancer tumour stage and the degree of registration in a population-based cancer registry].

UNLABELLED: Population-based cancer registries provide a large database of cancer cases which can be used for evaluation of cancer epidemiological and care-related questions. In particular, the latest projects in breast cancer screening and quality assured breast cancer diagnostics represent appropriate databases in the use of cancer registry data for further evaluation. For breast cancer the tumour stage distribution is a well suited, early available indicator for evaluating such interventions. The problem in using data from cancer registries occurs with the rather long time period until registration can be completed (up to 3 years). Thus, early usage of cancer registry data remains rather questionable. AIM OF THE STUDY: This analysis aims to show whether the distribution of breast cancer tumour stage depends on the completeness of registration and whether a valid estimate of the tumour stage distribution is possible at an early stage, on the basis of a not fully completed registration. METHODS: The cancer registry records all new cancer cases of the Federal State of Schleswig-Holstein. For the period from 1998 to the beginning of 2003 all breast cancer cases and their tumour stage distribution were extracted at three-month' intervals. Completeness of registration for each date was estimated on the basis of cancer data from the Federal State of Saarland. The expected number of breast cancer cases for Schleswig-Holstein was set to 100%. RESULTS: In total, 7,418 patients with new breast cancer were analysed. Already at a degree of 50% of registration a stable distribution of tumour stage could be observed. For example, the variability of the T1-category (tumour size < or = 2 cm) showed a maximum of three per cent in the range from 50% up to 100% completeness. Also for lymph nodes and distant metastases just a small degree of variability from one to three per cent points could be shown. A 75% completeness of breast cancer registration was established about six months after the end of the year of diagnosis. Complete registration could only be reached significantly later, approximately after two years. CONCLUSION: For the cancer registry of Schleswig-Holstein a significant relation of the tumour stage distribution in the degree of registration could not be detected. A stable distribution could be shown with a completeness of 50-75%. Hence, it appears to be methodically justified to analyse the tumour stage of breast cancer data with sufficient validity with a completeness of 75 %. The tumour stage distribution can be used as an early indicator (about six months after the end of the year of diagnosis) for evaluation of projects like mammography screening, quality management or research on medical care.

Breast↗

Single-cell nonphotochemical hole burning of ovarian surface epithelial carcinoma and normal cells.

Persistent spectral nonphotochemical hole-burning (NPHB) spectroscopy has recently been applied to dye molecules in cells. The sensitivity of NPHB to the nanoenvironment of the probe is well established. It has been shown that NPHB applied to bulk suspensions of cultured human cells can distinguish between normal and cancer cells. Thus, NPHB has potential as a diagnostic cancer tool. For this reason, the methodology is referred to as hole-burning imaging, by analogy with MRI. The optical dephasing time (T(2)) of the dye in hole-burning image replaces the proton T(1) relaxation time in MRI. In addition to the T(2) mode of operation, there are four other modes including measurement of the spectral hole growth kinetics (HGK). Reported here is that the selectivity and sensitivity of NPHB operating in the HGK mode allow for distinction between normal and carcinoma cells at the single-cell level. The ovarian cell lines are ovarian surface epithelial cells with temperature-sensitive large T antigens (analogously normal) and ovarian surface epithelial carcinoma (OV167) cells. The mitochondrial specific dye used was rhodamine 800 (Molecular Probes). This carbocationic dye is highly specific for the outer and inner membranes of mitochondria. In line with the results for bulk suspensions of the two cell lines, the hole-burning efficiency for OV167 cells was found to be significantly higher than that for normal cells. Theoretical analysis of the HGK data leads to the conclusion that the degree of structural heterogeneity for the probe-host configurations in OV167 cells is lower than in the normal cells. Possible reasons for this are given.

Epithelial Cells↗

Telomerase and cancer.

Telomerase, a eukaryotic ribonucleoprotein (RNP) complex, contains both an essential RNA and a protein reverse transcriptase subunit. By reverse transcription, the telomerase RNP maintains telomere length stability in almost all cancer cells. Over the past few years there has been significant progress in identifying the components of the telomerase holoenzyme complex and the proteins that associate with telomeres, in order to elucidate mechanisms of telomere length regulation. This review covers recent advances in the field including the use of telomerase in cancer diagnostics and an overview of anti-telomerase cancer therapeutic approaches.

Animals↗

Factors influencing behavioral intention regarding prostate cancer screening among older African-American men.

PURPOSE: To assess factors associated with perceptions of prostate cancer screening among African-American men aged > or = 55 years based upon items developed using the Preventive Health model (PHM). RESEARCH APPROACH: Focus group research and thematic coding using content analysis. SETTING: A large midwestern, private, nonprofit health system. PARTICIPANTS: African-American men aged > or = 55 years. Focus group 1 included 10 men who ranged in age from 55-87 years, with a mean age of 73.4 years. The 11 participants in focus group 2 ranged in age from 55-81 years, with a mean age of 68.7 years. METHODOLOGICAL APPROACH: Focus group questions were developed based on the conceptual framework of the PHM. African-American men aged > or = 55 years were randomly selected from the patient population of the healthcare system to participate in one of two focus groups. Content analysis was used to code the focus group transcripts. MAIN RESEARCH VARIABLES: Self-reported perceptions of prostate cancer screening. FINDINGS: Major themes emerging from the focus groups related to prostate cancer screening include: lack of knowledge regarding cancer, fear of cancer, confusion between prostate cancer screening and prostate cancer diagnostic tests, encouragement by others as motivation for cancer screening, intergenerational transfer of health information, lack of health insurance coverage as a barrier to prostate cancer screening and treatment, and limited availability of screening clinic hours during nonworking hours. INTERPRETATION: The information gained from this study could be used to develop interventions promoting informed and shared decision-making by patients and their providers regarding prostate cancer screening.

Black or African American↗

Cancer proteomics: Serum diagnostics for tumor marker discovery.

Cancer proteomics is an exciting field that is witnessing many new developments in recent years. It is hoped that these advances will result in decreased cancer death rates, which have not declined dramatically in the last several decades. Some of the problems with current tumor markers include the lack of sensitivity and specificity, factors that prevent their use in population-based screening of disease. Thus, there is an urgent need to identify novel biomarkers that can faithfully detect the disease state. As we are now in the post-genome era, many opportunities have been created. Genomic sequence data are available for human, as well as several other species. We are now poised to mine these data and to determine the functions of the encoded proteins constituting the human genome. Proteomics affords this opportunity by providing enhanced procedures and tools for discovery and also a framework for understanding these components in terms of pathogenesis. New technologies and improvements in existing methodologies will allow for the rapid growth in the identification and characterization of peptides and proteins that are unique to various clinical states. This technology can be successfully applied to clinical specimens for the identification of new tumor markers.

Algorithms↗