Cancer Patients In Different Stages Research Articles

Novel Therapies and Strategies to Overcome Resistance to Anti-HER2-Targeted Drugs.

Simple SummaryDrug resistance is the “Achilles’ heel” in current oncology. In this sense, the clinical management of HER2 breast carcinomas (tumors with overexpression/amplification of the ErbB2/HER2 oncogene) is still a challenge. Although a variety of anti-HER2 therapies (anti-HER2 antibodies, antibody–drug conjugates, and tyrosine kinase inhibitors) are available for these patients, the frequent appearance of innate and acquired tumor resistance to these treatments creates an urgent need to develop new and more effective therapeutic approaches. In this review, we discuss the most relevant clinical and pre-clinical advances in therapeutic strategies aimed at overcoming drug resistance in HER2 breast cancer patients in different stages of the disease.The prognosis and quality of life of HER2 breast cancer patients have significantly improved due to the crucial clinical benefit of various anti-HER2 targeted therapies. However, HER2 tumors can possess or develop several resistance mechanisms to these treatments, thus leaving patients with a limited set of additional therapeutic options. Fortunately, to overcome this problem, in recent years, multiple different and complementary approaches have been developed (such as antibody–drug conjugates (ADCs)) that are in clinical or preclinical stages. In this review, we focus on emerging strategies other than on ADCs that are either aimed at directly target the HER2 receptor (i.e., novel tyrosine kinase inhibitors) or subsequent intracellular signaling (e.g., PI3K/AKT/mTOR, CDK4/6 inhibitors, etc.), as well as on innovative approaches designed to attack other potential tumor weaknesses (such as immunotherapy, autophagy blockade, or targeting of other genes within the HER2 amplicon). Moreover, relevant technical advances such as anti-HER2 nanotherapies and immunotoxins are also discussed. In brief, this review summarizes the impact of novel therapeutic approaches on current and future clinical management of aggressive HER2 breast tumors.

Oxysterols in cancer management: From therapy to biomarkers.

Oxysterols are oxidized derivatives of cholesterol, both endogenous and exogenous. They have been implicated in numerous pathologies, including cancer. In addition to their roles in carcinogenesis, proliferation, migration, apoptosis, and multiple signalling pathways, they have been shown to modulate cancer therapy. They are known to affect therapy of hormonally positive breast cancer through modulating oestrogen receptor activity. Oxysterols have also been shown in various in vitro models to influence efficacy of chemotherapeutics, such as doxorubicin, vincristine, cisplatin, 5-fluorouracil, and others. Their effects on the immune system should also be considered in immunotherapy. Selective anti-cancer cytotoxic properties of some oxysterols make them candidates for new therapeutic molecules. Finally, differences in oxysterol levels in blood of cancer patients in different stages or versus healthy controls, and in tumour versus non-tumour tissues, show potential of oxysterols as biomarkers for cancer management and patient stratification for optimization of therapy. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.

SENSITIVITY OF S+ERUM PROTEINS OF GI CANCER PATIENTS TO CHEMOTHERAPY COURSES

Gastrointestinal cancers (GI) are one of the most abundant types of cancers among the world population, though statistical data indicate that in eastern Asia these types of cancer occur 4 times more often than in Western Europe. Absence of treatment of bacterial infections, obesity, and lack of vegetable food in a diet can be the case of GI cancer. All pathologies are inevitably connected to the changes in cell cycle, abnormal protein amount and their dysfunction. Serum proteins are widely used as an additional source of information about body condition, also changes in protein composition can point out the mechanism of disease development and effectiveness of treatment. In the presented work we studied protein composition of GI cancer patients in different stages of cancer development, after and before chemotherapy and compared these data to protein composition of healthy control group of voluntaries. Treatment of patients was performed according the guidelines appropriate for the GI cancer. Association of the effectiveness of treatment at the different stages of chemotherapeutic courses and changes of protein composition of blood serum has been assessed. Proteins composition was studies by SDS-PAGE electrophoresis and densitometry analysis. Experimentally gained molecular and statistical information exposed the most vulnerable groups of proteins affected by chemotherapeutic agents indicating targets for searching new biomarkers for treatment effectiveness. Research involving human patients performed in accordance with the requirements of the Council of Europe Convention on Human Rights and Biomedicine, Biomedical Research, as well as the UNESCO Declaration of Bioethics and Human Rights.

SENSITIVITY OF SERUM PROTEINS OF GI CANCER PATIENTS TO CHEMOTHERAPY COURSES

Gastrointestinal cancers (GI) are one of the most abundant types of cancers among the world population, though statistical data indicate that in eastern Asia these types of cancer occur 4 times more often than in Western Europe. Absence of treatment of bacterial infections, obesity, and lack of vegetable food in a diet can be the case of GI cancer. All pathologies are inevitably connected to the changes in cell cycle, abnormal protein amount and their dysfunction. Serum proteins are widely used as an additional source of information about body condition, also changes in protein composition can point out the mechanism of disease development and effectiveness of treatment. In the presented work we studied protein composition of GI cancer patients in different stages of cancer development, after and before chemotherapy and compared these data to protein composition of healthy control group of voluntaries. Treatment of patients was performed according the guidelines appropriate for the GI cancer. Association of the effectiveness of treatment at the different stages of chemotherapeutic courses and changes of protein composition of blood serum has been assessed. Proteins composition was studies by SDS-PAGE electrophoresis and densitometry analysis. Experimentally gained molecular and statistical information exposed the most vulnerable groups of proteins affected by chemotherapeutic agents indicating targets for searching new biomarkers for treatment effectiveness. Research involving human patients performed in accordance with the requirements of the Council of Europe Convention on Human Rights and Biomedicine, Biomedical Research, as well as the UNESCO Declaration of Bioethics and Human Rights. Keywards: Gastrointestinal cancer, chemotherapy, proteins, biomarkers.

Coupling metal-organic framework nanosphere and nanobody for boosted photoelectrochemical immunoassay of Human Epididymis Protein 4

A “signal-on” photoelectrochemical (PEC) immunosensor for highly sensitive detection of Human Epididymis Protein 4 (HE4), a new serum biomarker of ovarian cancer with small molecular weight, was fabricated by coupling the porphyrin-based metal-organic framework (MOF) nanosphere (nPCN-224) and Nanobody (Nb). To label the Nb, the nPCN-224 with an average size of 160–200 nm was prepared by solvothermal method. The mechanism for the photocurrent generation of nPCN-224 was systematically investigated, showing that the dissolved O2 in aqueous solution participated in the charge separation and transport during the photoelectric conversion by generating O2˙-, which resulted in a 6-fold enhanced photocurrent by using ascorbic acid as the O2 ˙- scavenger. Moreover, the inherent structural porosity of nPCN-224 demonstrated advantage for reactant accessibility. Due to the superior properties of nPCN-224, and the high specificity and affinity of Nbs, the immunosensor exhibited a broad detection range from 1.00 pg mL−1 to 10.0 ng mL−1 and a detection limit of 0.560 pg mL−1, lower than most methods reported before. The immunosensor could clearly distinguish ovarian cancer patients in different stages from healthy individuals, and the as-obtained results matched well with those by traditional electrochemiluminescence immunoassay method from the hospital. This work would open a new avenue for PEC immunosensors in clinical diagnostics and evaluation of potential clinical efficacy.

A Study on Challenges to Health Care Delivery Faced by Cancer Patients in India During the COVID-19 Pandemic.

IntroductionAccess to health care and care delivery during the COVID-19 pandemic may be challenging for cancer patients. Several guidelines have been developed, which recommend treatment adjustments depending on the site of cancer, grade, and stage. However, few studies in India and across the globe have looked into the real challenges faced by cancer patients and assessed the effectiveness of the adopted interventions. This study was undertaken with the objective to study the challenges faced by cancer patients in India during the COVID-19 pandemic.Materials and MethodsThis was a cross-sectional study undertaken between May 1, 2020 and May 15, 2020. A link to a prestructured questionnaire was sent through email to 100 randomly selected cancer patients in different stages of treatment and follow-up. Data were decoded and entered in Microsoft Excel 2010 and analyzed using descriptive statistics.ResultsSlot availability for teleconsultation, network issues, deferral of radiotherapy dates and long waiting hours beyond appointment time, transportation problems from residence to hospital, restriction of visitors/attendants, deferral of surgery, deferral of tumor boards, delay and deferral of advice of the nutritionist, problems faced in extension of visa, unavailability of peer group support services and psychological counseling sessions, difficulty in maintaining precautionary measures, availability of chemotherapy medications and availability of chemotherapy slots in day care were cited as problems faced by cancer patients. Majority (91.7%) of the study respondents mentioned an increase in their anxiety levels.ConclusionAs highlighted in the study, cancer patients faced challenges in cancer care delivery during the COVID-19 pandemic. This study suggests the need for larger studies on cancer patient care during a pandemic.

The Potential of the Quick Detection of Selectins Using Raman Spectroscopy to Discriminate Lung Cancer Patients from Healthy Subjects

This study aimed at determining the concentration of P-selectins in lung cancer patients in different stages and healthy subjects. Then, the ability of the methodology developed to discriminate the existence of lung cancer was also evaluated. Serum spectra were obtained using Raman spectroscopy (RS). Blood samples were taken from subjects divided into two groups: group 1—comparing data from 22 patients clinically diagnosed with cancer before versus after medical intervention; group 2—comparing data from 10 palliative patients versus 17 healthy volunteers. The RS analysis of the samples revealed the presence of five very similar peaks in both groups 1 and 2. This leads to the conclusion that a medical intervention in cancer cases gives results comparable to those obtained from healthy subjects. The study indicates that the use of Raman spectroscopy can produce a better classification of cancer patients. However, diagnostically the results have not been statistically significant, probably due to the limited number of samples gathered. A larger number of samples would be required for future verification.

Unmet needs of Italian cancer patients in different stages of the disease and care process.

Assessing patients' unmet supportive care needs is essential in order to prioritize areas of cancer care that require improvement. The aim of the present cross-sectional study was to compare the unmet needs of cancer patients in different stages of the disease and care process (diagnosis, treatments following diagnosis, follow-up and/or rehabilitation, relapse/recurrence, progression of the disease, and palliative care). The research focused on patients from 7 oncology units of the same geographic region (Tuscany, a region of central Italy) in the same period of time regardless of primary tumor site. A total of 752 patients filled in the Needs Evaluation Questionnaire and the Psychological Distress Inventory. We observed high rates of cancer patients who expressed unmet needs, especially in the areas of information and relational and material needs. The multiple regression models showed a direct correlation between psychological distress and extent of unmet needs. Individual unmet needs had significantly different entities at diverse phases. The present study confirmed the dynamic nature of needs of cancer patients, highlighting some critical aspects in different stages of the care process on which to concentrate attention and resources and suggesting the usefulness of periodic and repeated assessments of principal needs.

Abstract P5-18-03: Relationships among breast symmetry, appearance investment, and body image dissatisfaction in breast cancer patients undergoing reconstruction

Abstract Purpose: Reconstruction as part of treatment for breast cancer is aimed at mitigating body image concerns post-mastectomy. Although algorithms are increasingly being developed to objectively assess breast reconstruction outcomes, previous research has not evaluated associations between objectively quantified breast aesthetic appearance and patient-reported body image outcomes. Further, the role appearance investment plays in a patient's body image is not well understood. We examined the extent to which objectively quantified breast symmetry and appearance investment were associated with body image dissatisfaction in patients undergoing cancer-related breast reconstruction. Method: Breast cancer patients in different stages of reconstruction (n=190) completed self-report measures of appearance investment and body image dissatisfaction. Vertical extent and horizontal extent symmetry values, which are indicators of breast symmetry across the vertical axis, were calculated from clinical photographs. Associations among symmetry, appearance investment, body image dissatisfaction, and patient clinical factors were examined. Multiple regression was used to evaluate the association of symmetry and appearance investment with body image dissatisfaction. Results: Vertical extent symmetry, but not horizontal extent symmetry, was associated with body image dissatisfaction. Multiple regression results indicated that decreased vertical extent symmetry (β = -0.24, p <0.01) and increased appearance investment (β = 0.37, p <0.001) were significantly associated with greater body image dissatisfaction while controlling for clinical factors.Conclusions: Our findings suggest that quantitatively measured reconstruction outcomes and appearance investment both significantly contribute to an understanding of patient-reported body image satisfaction during breast reconstruction treatment. Future studies are encouraged to utilize algorithms assessing breast aesthetic appearance and to consider patient values as predictors of body image outcomes. Symmetry Predicting Body Image Dissatisfaction Controlling for Clinical Factors Body Image Dissatisfaction (β)VE Symmetry-0.24**Appearance investment (ASI-R)0.37*** Clinial factors controlled for BMI-0.01Prior chemotherapy0.19Prior radiation therapy0.08Prior complications0.06Reconstruction timing (ref: Immediate) Delayed0.06Reconstruction type (ref: Implant) Autologous-0.01Mixed type0.09Reconstruction Stage (ref: Pre-surgery) Intermediate-0.06Final-0.15*p<.05, **p<.01, ***p<.001; ref = reference group; Note ASI-R = Appearance Schemas Inventory-Revised Citation Format: Nicklaus KM, Teo I, Reece GP, Huang S-C, Mahajan K, Andon J, Khanal P, Sun CS, Merchant FA, Markey MK, Fingeret MC. Relationships among breast symmetry, appearance investment, and body image dissatisfaction in breast cancer patients undergoing reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-18-03.

Body image dissatisfaction in patients undergoing breast reconstruction: Examining the roles of breast symmetry and appearance investment.

Reconstruction as part of treatment for breast cancer is aimed at mitigating body image concerns after mastectomy. Although algorithms have been developed to objectively assess breast reconstruction outcomes, associations between objectively quantified breast aesthetic appearance and patient-reported body image outcomes have not been examined. Further, the role of appearance investment in explaining a patient's body image is not well understood. We investigated the extent to which objectively quantified breast symmetry and patient-reported appearance investment were associated with body image dissatisfaction in patients undergoing cancer-related breast reconstruction. Breast cancer patients in different stages of reconstruction (n=190) completed self-report measures of appearance investment and body image dissatisfaction. Vertical extent and horizontal extent symmetry values, which are indicators of breast symmetry, were calculated from clinical photographs. Associations among breast symmetry, appearance investment, body image dissatisfaction, and patient clinical factors were examined. Multi-variable regression was used to evaluate the extent to which symmetry and appearance investment were associated with body image dissatisfaction. Vertical extent symmetry, but not horizontal extent symmetry, was associated with body image dissatisfaction. Decreased vertical extent symmetry (β=-.19, P<.05) and increased appearance investment (β=.45, P<.001) were significantly associated with greater body image dissatisfaction while controlling for clinical factors. Breast symmetry and patient appearance investment both significantly contribute to an understanding of patient-reported body image satisfaction during breast reconstruction treatment.

Emotional distress and dysfunctional illness perception are associated with low mental and physical quality of life in Chinese breast cancer patients

BackgroundTo evaluate the relationship between quality of life (QOL) and physical as well as psychological variables in Chinese breast cancer patients.MethodsThis multicenter cross-sectional study enrolled 254 Chinese breast cancer patients in different stages and treatment phases. They answered standard instruments assessing QOL (EORTC), somatic symptom severity (PHQ-15), depression (PHQ-9), anxiety (GAD-7), health-related anxiety (WI-7), illness perception (BIPQ), and sense of coherence (SOC-9). Canonical correlation was applied to identify the strongest correlates between the physical, emotional and social QOL scales and the physical and psychological variables.ResultsIn our sample, a low global QOL was significantly associated with the following physical and psychological variables: symptom-related disability (Karnofsky Index) (r = .211, p < .01), somatic symptom severity (r = −.391, p < .001), depression (r = −.488, p < .001), anxiety (r = −.439, p < .001), health-related anxiety (r = −.398, p < .001), dysfunctional illness perception (r = −.411, p < .001), and sense of coherence (r = .371, p < .001). In the canonical correlation analysis, high somatic symptom severity, depression, anxiety, dysfunctional illness perception, and low sense of coherence showed the strongest correlations with low physical, emotional and social functioning. The first three significant canonical correlations between these two sets of variables were .78, .56, and .45.ConclusionsQOL in Chinese breast cancer patients is strongly associated with psychological factors. Our results suggest that Chinese physicians and nurses should incorporate these factors into their care for women with breast cancer to improve patients’ QOL.

Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy

Depression and anxiety, the most important psychological disorders in cancer patients, have now been considered as psychoneuroimmunological disorders, in which peripheral immune activation, through the release of proinflammatory cytokines, is implicated in the variety of behavioral, neuroendocrine and neurochemical alterations associated with these disorders. Along with the tumor itself, cancer treatment can also contribute to exacerbate the production of proinflammatory cytokines. This study aimed to investigate whether proinflammatory cytokine levels are related to depression and anxiety in CRC patients in different stages of the antitumor therapy We evaluated 60 patients in three stages of antitumor therapy (Pre-chemotherapy, Under-chemotherapy and Post-chemotherapy, n=20 in each group) and 20 healthy volunteers by the Hospital Anxiety and Depression Scale (HADS). Serum levels of cytokines were measured by CBA. Depression and/or anxiety were found at clinically relevant levels in CRC patients during all antitumor therapy. Patients in pre-chemotherapy group exhibited the highest concentrations of pro-inflammatory cytokines and the lowest levels of IL-10. In latter stages of treatment, cytokines reached levels similar to the control group. Correlation analysis between HADS score and cytokine serum levels revealed positive associations of anxiety and/or depression with IL-1β, IL-6, IL-8, and TNF-α, and a negative correlation with IL-10, suggesting that cytokines are involved in the pathophysiology of these psychological disorders in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of new therapeutic strategies to assist in alleviating such symptoms in cancer patients.

Inventory survey and influence factor analysis on the sleep quality of cervical cancer patients

Objective To understand about the sleep quality of cervical cancer patients, investigate the correlative factors that influence sleep quality, so as to provide the basis for improving the sleep quality of cervical cancer patients. Methods Cervical cancer patients whose postoperative tissue pathology was diagnosed as FIGO stage I and II were selected.7 days before and after operation, 1 month after operation in the follow-up visit (3 times), demographic questionnaire form, PSQI, CES-D self-rating depression scale, POMS-SF self-rating anxiety scale and cancer therapy function questionnaire (FACT-G) were used to have investigation and analysis on cervical cancer patients and hospitalized benign tumor (uterine fibroid) patients in the same term. Results Cervical cancer patients had no statistical difference from uterine fibroid patients on demographic questionnaire form.In different stages, PSQI aggregate score, CES-D depression, POMS-SF anxiety and FACT-G scores to the cervical cancer patients 7 days before and after operations, follow-up visit 1 month after operation had no significant statistical difference. However, compared with uterine fibroid patients, PSQI aggregate score, CES-D depression, POMS-SF anxiety and FACT-G scores of cervical cancer patients were higher 7 days before and after operations, follow-up visit 1 month after operation.However, the living quality score of FACT-G was lower than uterine fibroid patients, and the difference had statistical significance. Multivariate Logistic regression analysis indicated that marital status, educational level, working condition, family economic status, medical payment method, disease diagnosis and staging, pain score, depression, anxiety and living quality were obviously associated with the sleep disorder of cervical cancer patients. Conclusion The sleep quality of cervical cancer patients in different stages before operation and in the early stage after operation was inferior to benign tumor patients.In addition, sleep disorder occurrence rate of cervical cancer patients is higher.Sleep disorder can not only result in depression and anxiety easily, but also influence the living quality of patients. Key words: Cervical cancer; Sleep quality; Sleep disturbance

P-280 - The molecular profile of colon cancer cells

Introduction: Colon cancer is the third most commonly diagnosed cancer in both women and men, while it accounts for approximately 10-15% of all cancer deaths each year. People diagnosed with colon cancer at its earliest stage have higher survival (five-year or more) than those diagnosed at latest stages. Therefore the identification of new biomarkers, which constitute in early detection, is of primary importance for scientists. The present study aimed to analyze the gene expression profile of colon circulating tumor cells and compare it with profiles of other cancer types. Methods: Blood samples were collected from 8 colon cancer patients in different stages of the disease and CTCs were isolated using enrichment isolation protocols. RNA was extracted from the above cells as well as from commercial cell lines representing the same type of cancer, provided by ECACC. The RNA was used as template for microarray experiments in the Human MI ReadyArray platform, while a universal reference RNA was used as reference. The microarray data were normalized using background subscription and analysis of variance was performed. Genes with Log2ratios >2 and repeatable results were selected for clustering analysis. The above data were then compared with data from other cancer types. Results: The microarray experiments in colon CTCs revealed more than 50 genes that were overexpressed, included transcription factors (ATF7), cytokine ligands (CCL5), kinases (STK10) and genes involved in other procedures. In addition over expression was observed for other genome regions including transposable elements (LINE-1), tRNAs or snRNAs. The clustering analysis including the commercial cell lines did not revealed common gene expression patterns. In commercial cell lines there was observed over expression mainly in genes correlated with cell adhesion (CDH3, ANXA3 etc.). Genes correlated with cell adhesion, cell motility and cell invasion, were also overexpressed in other types of cancer (prostate, breast). Conclusion: The present demonstrated that in colorectal cancer, the gene expression profile is different between CTCs and established colon cells. Furthermore, in colon CTCs there was observed over-expression in genes, which were not detected in other cancer types. Therefore, the above genes should be used as potential biomarkers or after evaluation as drugable targets. Further studies, in more samples, are imperative to confirm all the above and be able to use at clinical level.

Abstract P6-08-08: Expression and role of ING3 gene in breast cancer

Abstract Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p&amp;lt;0.001 and p&amp;lt;0.001, respectively). ING3 expression in tumor tissues of the patients with advanced disease (stage 3-4) was detected higher than ones with early stage disease and it was found to be statistically significant at the border (p=0.048). Moreover, there were no significant changes when ING3 gene expressions were compared with c-erbB2 (Receptor tyrosine-protein kinase erbB-2) status and tumor grade (p&amp;gt; 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

Targeting the heat shock response in combination with radiotherapy: Sensitizing cancer cells to irradiation-induced cell death and heating up their immunogenicity

Radiotherapy represents an essential treatment option for the majority of cancer patients in different stages of their disease. Physical achievements of the recent years led to the implementation of high precision treatment planning procedures, and image-guided dose delivery is current state of the art. Yet, radiotherapy still faces several limitations with cancer intrinsic radioresistance being a key driver of therapeutic failure. Accordingly, the mechanisms orchestrating radioresistance and their therapeutic targeting by combined modality approaches are in the center of attention of numerous radiation oncologists. In the present review, we summarize and discuss therapeutic approaches that exploit the heat shock response, either by hyperthermia or by pharmacological heat shock protein inhibition, in combination with radiotherapy. These strategies appear particularly promising, since they sensitize cancer cells to irradiation-induced cell death and at the same time have proven the potential to promote systemic anti-tumor immune mechanisms, which may target not only locally surviving tumor cells, but also distant out-of-field metastases.

P-0205 - Cytokines, Depression and Anxiety in Colorectal Cancer Patients in Different Stages of the Antitumor Therapy

Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality in the world. Depression and anxiety are the most prevalent psychological disorders in patients with CRC. This study aimed to investigate whether serum cytokine levels correlate with anxiety and depression in colorectal cancer patients in different stages of the antitumor therapy. Methods: A total of 100 subjects were divided in 5 groups. Group 1: Healthy volunteers free of any psychiatric or immune system disease (n = 20); Group 2: Patients with colorectal cancer who did not undergo surgical resection of tumor (n = 20); Group 3: Patients who underwent surgical resection and who did not start adjuvant therapy (n = 20); Group 4: Patients undergoing chemotherapy (for about 3 months) (n = 20); Group 5: Patients who have completed adjuvant chemotherapy regimen (about 6 months after the end of treatment) (n = 20). Depression and anxiety were analyzed using the Hospital Anxiety and Depression Scale (HADS) and serum levels of IL-1, IL-6, IL-8, IL-10, IL-12, TNF-&agr; and TGF-&bgr; were measured by CBA. Results: Clinically relevant levels of anxiety and/or depression were found in all CRC patients in different stages of the antitumor therapy. Serum levels of the proinflammatory cytokines IL- 1, IL- 6, IL- 8 and TNF- &agr; were increased in CRC patients in pre and postoperative stages. However, these levels were reduced during and after chemotherapy. Furthermore, we found decreased levels of IL-10 in serum of patients in CRC patients in pre and postoperative stage. By analyzing the correlation between HADS scores and serum cytokine levels, we observed a positive association of anxiety and/or depression with concentrations of IL-1, IL-6, IL-8 and TNF-&agr; and negative compared to levels serum IL-10 in different stages of the antitumor therapy. Conclusion: These results indicate a link between serum levels of pro-inflammatory cytokines, anxiety and depression in CRC patients, suggesting that cytokines are involved in the pathophysiology of these comorbidities.

Measuring individual quality of life in patients receiving radiation therapy: the SEIQoL-Questionnaire

Quality of life (QoL) is one of the most important outcomes in cancer care. Although a number of instruments to measure health-related QoL (HRQoL) exist, there are few suitable instruments to measure individual QoL. The best established instrument is the Schedule for the Evaluation of Individual Quality of Life (SEIQoL). The disadvantage of this questionnaire is its use of semi-structured interviews, which are very time-consuming. The purpose of our study was to transform the SEIQoL into an economical instrument that can be used in clinical trials with large samples. We developed the SEIQoL-Questionnaire (SEIQoL-Q) on the basis of the SEIQoL-Direct Weighting (SEIQoL-DW) by transforming the interview guide into a written questionnaire. Patients (N=1,108) in all three phases of radiation treatment (first consultation, ongoing irradiation, and aftercare) were asked to complete the SEIQoL-Q and the European Organization for Research and Treatment of Cancer QLQ-C30. While the average HRQoL measured by the QLQ-C30 was 55.6, the average SEIQoL-Q index was 59.6. The most important life domain was "physical health," followed by "emotional well-being" and "family." Patients attributed the highest level of satisfaction to "home/housing," followed by "family" and "partnership." Male patients were shown to have a significantly better QoL than females. The SEIQoL-Q index correlates moderately with the QLQ-C30 functioning scale "global quality of life" [r=.42 (p<.001)]. According to our findings, the SEIQoL-Q appears to be a feasible and economical instrument for use in quantitative research among cancer patients in different stages of their disease.

A phylogenetic model for understanding the effect of gene duplication on cancer progression.

As biotechnology advances rapidly, a tremendous amount of cancer genetic data has become available, providing an unprecedented opportunity for understanding the genetic mechanisms of cancer. To understand the effects of duplications and deletions on cancer progression, two genomes (normal and tumor) were sequenced from each of five stomach cancer patients in different stages (I, II, III and IV). We developed a phylogenetic model for analyzing stomach cancer data. The model assumes that duplication and deletion occur in accordance with a continuous time Markov Chain along the branches of a phylogenetic tree attached with five extended branches leading to the tumor genomes. Moreover, coalescence times of the phylogenetic tree follow a coalescence process. The simulation study suggests that the maximum likelihood approach can accurately estimate parameters in the phylogenetic model. The phylogenetic model was applied to the stomach cancer data. We found that the expected number of changes (duplication and deletion) per gene for the tumor genomes is significantly higher than that for the normal genomes. The goodness-of-fit test suggests that the phylogenetic model with constant duplication and deletion rates can adequately fit the duplication data for the normal genomes. The analysis found nine duplicated genes that are significantly associated with stomach cancer.

Abstract PD6-1: Tumor spheres growing from peripherally circulating tumor cells exhibit stem cell features

Abstract Background: Among the cells that are disseminated from a malignant tumor only very few are capable to resettle in distant organs and grow into life-threatening metastases. Therefore, the question arises how and whether such cells which have the potential to grow into metastases can be detected. It has been shown that a subpopulation of cells from breast cancer tissue can form so-called mammospheres with stem cell features. Here we show that such tumor spheres can also be grown from peripherally circulating tumor cells from breast cancer patients in different stages of disease Materials and Methods: Using a nondissipative approach with only one enrichment step of red blood cell lysis, the cells from the pellet, containing the white blood cells together with the putative tumor cells were cultured under conditions favoring the growth of epithelial cells. At 7, 14 and 21days the cell cultures were inspected for the appearance of spheroids staining with anti-EpCAM, anti-CD24 and anti-CD44 antibody and.expressing ALDH1. Results: Peripherally circulating cells from patients with malignant tumors in different stages of disease were analyzed for the presence of circulating epithelial tumor suspect cells and the frequencies of tumorspheres. Tumorspheres could so far be grown from 79% of 36 patients in whom more than 1700/ml epithelial tumor suspect cells were detected. Numbers of tumorspheres varied from 1 to 29 /ml and correlated with the aggressiveness of the tumor. Surprsingly the numbers were highest in patients after surgery who had not yet received any systemic therapy. The size of the spheres increased from day 7 to day 21. The spheres were negative for CD24 and positive for CD44. They highly express ALDH1 and thus exhibite typical features of stem cells. Conclusion: Here, we demonstrate that the circulating tumor cells, detected in our approach contain a subpopulation with stem cell-like properties capable of growing into tumorspheres. The frequency and growth potential of cells capable of forming spheres seems to be dependent from the properties of the primary tumor. The possibility to grow tumorspheres from peripherally circulating tumor cells may open up a new field, where the relevant cells with stem cell properties from individual patients can now be specifically analysed further for genetic endowment, transcriptional activity, heterogeneity and stem cell markers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-1.