Common Cancer Disease Research Articles

Clinical utility of an endorectal MRI-guided prostate probe: preliminary examinations

Abstract Prostate cancer (PCa) is one of the most common cancer diseases in men in the western countries [1]. Besides the palpation, and the amount of prostate-specific-antigen’s (PSA) inside the blood, the current diagnostic imaging technologies are not appropriate. Early diagnosis defining the exact tumor location, spread and margins could make efficient targeted biopsies and image-guided surgery. A multimodal imaging technique containing a transmit-receive surface coil for anatomical MR imaging, a (S)PET detector module, consisting of silicon photomultipliers (SiPM), for functional imaging and an ultrasound (US) probe are placed as close as possible to the prostate designed as an endorectal tube to increase sensitivity and spatial resolution. All materials that are used are non-magnetic. Advantages of the SiPM are diversified, like non-sensitive to magnetic fields, higher gain (105–106) than standard avalanche photodiodes (APD), good timing properties and compactness. The PET detector should reach approximately 1mm3 spatial resolution together with 60ps FWHM Time-of-Flight resolution and a high efficiency to reduce scanning time and injected dose. A home-made transmit-receive coil surrounding the PET module improves signal-to-noise-ratio (SNR) with respect to standard coils will be present. The system will be used as a MRI-insert and be able to visualize anatomic and metabolic information together. The US-probe is guiding examination for correct overlapping of the multimodal images. This procedure will save time, costs and the need of co-registration. By combining all advantages of each system, it will necessarily update the non-invasive treatment of PCa. The system is adapted and tested to a 3 Tesla MR scanner called Trio A Tim system and Allegra system from the company Siemens healthcare with a larmor frequency of 123.2 MHz and an input of 50 Ω free from artifacts. First results on homogeneity of the transmit-receive coil will be presented. Preliminary measurements showing the proposed device is challenging but feasible.

Drug development for breast, colorectal, and non-small cell lung cancers from 1979 to 2014.

Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites. A total of 411 drugs met the inclusion criteria for breast cancer, 246 drugs met the inclusion criteria for colorectal cancer, and 315 drugs met the inclusion criteria for non-small cell lung cancer. Attrition rates were 83.9% for breast cancer, 87.0% for colorectal cancer, and 92.0% for non-small cell lung cancer drugs. In the case of non-small cell lung cancer, there was a trend toward higher attrition rates for targeted monoclonal antibodies compared with other agents. No tumor site-specific differences were noted with regard to cytotoxic chemotherapy, immunomodulatory, or small molecule kinase inhibitor drugs. Drugs classified as "others" in breast cancer had lower attrition rates, primarily due to the higher success of hormonal medications. Mean drug development times were 8.9 years for breast cancer, 6.7 years for colorectal cancer, and 6.6 years for non-small cell lung cancer. Overall oncologic drug attrition rates remain high, and drugs are more likely to fail in later-stage clinical trials. The refinement of early-phase trial design may permit the selection of drugs that are more likely to succeed in the phase 3 setting. Cancer 2017;123:4672-4679. © 2017 American Cancer Society.

Analysis of an electronic methods for nasopharyngeal carcinoma: Prevalence, diagnosis, challenges and technologies

ContextNasopharyngeal Carcinoma (NPC) is a category of cancer in the head and neck regions, and this cancer prevails in the throat area amongst the pharynx and nasal cavity. This NPC represent major health problem in Malaysia, being the fourth most common tumor among Malaysians and third most common cancer disease among Malaysian men. NPC is emphatically connected with Epstein-Barr Virus (EBV) and happens at the back of the nose. ObjectivesThe overall objective of this research is to discuss the prevalence of NPC in selected regions with a focus on Asia Pacific and Malaysia in particular, the categories, severities, symptoms and the existing electronic methods of investigating NPC symptoms. The research also identifies the weaknesses and strengths of the existing methods as inputs for propose improvement. Most part of the study reviewed the current approaches and techniques that are being proposed in other literatures in order to improve the process of investigating NPC. The study critically evaluates these different methods and the problems associated with them. This study provides some review of literatures indicating relationship between cancer milestones configuration and some NPC patient’s attributes. MethodsThis research presents a detailed description of image based NPC, NPC imagery techniques and image types. Next, continue to NPC segmentation, which includes modelling of NPC detection, and subsequently followed by a NPC image classification process. Finally, the research paper discussing the meaning and impact of approaches and the contribution of researchers in this area. The different of NPC symptoms and their basic method of diagnosis were briefly explained. The basic diagnostic procedure is depicted with six procedures where a patient undergoes if he or she is reported with NPC. The six procedures include Trans oral mirror examination, EBV Serology, Circulating EBV DNA in plasma (Plasma DNA), Nasoendoscopy, Biopsy and NP Screen™. FindingThe strengths and weaknesses of the existing methods are identified and identification model for NPC is proposed. The lesson learned from other methods were evaluated and incorporated into proposed model. This study further describes that segmentation, classification and predication of NPC based on many methods Additionally, a literature survey on segmentation, classification and predication of NPC based on real studies has been discussed.

Intraoperative Ultrasound as a Screening Modality for the Detection of Liver Metastases during Resection of Primary Colorectal Cancer - A Systematic Review.

Colorectal cancer (CRC) is one of the most common cancer diseases worldwide. One in 4 patients with CRC will have a disseminated disease at the time of diagnosis and often in the form of synchronous liver metastases. Studies suggest that up to 30% of patients have non-recognized hepatic metastases during primary surgery for CRC. Intraoperative ultrasonography examination (IOUS) of the liver to detect liver metastases was considered the gold standard during open CRC surgery. Today laparoscopic surgery is the standard procedure, but laparoscopic ultrasound examination (LUS) is not performed routinely. Aim To perform a systematic review of the test performance of IOUS and LUS regarding the detection of synchronous liver metastases in patients undergoing surgery for primary CRC. Method The literature was systematically reviewed using the search engines: PubMed, Cochrane, Embase and Google. 21 studies were included in the review and the key words: intraoperative ultrasound, laparoscopic ultrasound, staging colon and rectum cancer. Results Intraoperative ultrasound showed a higher sensitivity, specificity, positive predictive value and overall accuracy for the detection liver metastases during surgery for primary CRC, compared to preoperative imaging modalities (ultrasound, computed tomography (CT) and contrast-enhanced computed tomography (CE-CT)). LUS showed a higher detection rate for liver metastases compared to CT, CE-CT and magnetic resonance imaging (MRI). Conclusion This systematic review found that both IOUS and LUS had a higher detection rate regarding liver metastases during primary CRC surgery, especially liver metastases<10 mm in diameter, when compared to US, CT, CE-CT and MRI.

B32 - HER-2 in gastric cancer: a single institution experience

Gastric cancer is the fourth most common cancer disease worldwide and it's the second leading cause of cancer-related death. The study of HER-2 expression and the use of targeted agent trastuzumab have improved the prognosis of many patients. This abstract aims to show a casuistry of patients with gastric cancer related with their HER-2 expression. From May 2010 to November 2015 we observed 157 cases of patients with gastric cancer. Median age was 69,2 years (range 26,7-88 years), 116 were male and 41 were female. At diagnosis 19 patients had I stage disease, 15 patients II stage, 69 patients III stage and 54 patients were metastatic (IV stage). Globally we treated 84 metastatic patients. Among these HER-2 status was not assessable in 34,5% (n 29) because of Performance Status, comorbidities and age of patients. We tested 55 patients (65,5%): of these 72,7% were negative (n 40), 27,3% were positive (n 15). This percentage is higher than literature, maybe for the small number of patients of our casuistry. HER-2 expression was higher in intestinal-type cancer (8 of 23 patients, 34,8%). In relation of gastric site the highest percentage is in cardia (5 of 11 patients, 45,5%), the lowest in antrum (4 of 21, 19%). We treated with chemotherapy 30 of 40 patients HER-2 negative and with chemotherapy and trastuzumab 15 of 15 patients HER-2 positive. The chemotherapy regimen used for HER-2 positive patient were: cisplatin + 5-fluorouracil + trastuzumab (6 patients), weekly PFL (cisplatin, 5-fluorouracil, leucovorin) + trastuzumab (4 patients) and cisplatin + capecitabine + trastuzumab (5 patients). Among all treated patients, the Progression Free Survival was 3,4 months for HER-2 negative subgroup and 9,11 months for HER-2 positive. The Overall Survival was 7,7 months for HER-2 negative group and 13,7 months for HER-2 positives ones. It's interesting to notice that we are treating a young man 36 years old since 2011 with trastuzumab, without any signs of progression. This man has cardia carcinoma, intestinal-type, metastatic at adrenal gland and liver. These data, despite the little sample, confirm how the prognosis of HER-2 positive patients treated with trastuzumab is globally better than HER-2 negative, in agreement with literature.

A Survey on Prescription Pattern for Patient of Kidney Diseases

Kidney disease is a general term for any damage that reduces the functioning of the kidney. It can also cause other problems that can harm our health. So. The objective of this study is to explore the pattern and practice of medicine use among the patients of kidney diseases to manage these diseases. To perform this study a survey was conducted among the kidney patients of six randomly selected private hospitals of Dhaka &amp; Sirajganj city of Bangladesh. A total of 82 prescriptions were collected within March 2016 to April 2016, of which 60 were selected for the study based on their diagnostic findings of kidney diseases. All the prescription were prescribed by kidney specialist reflecting the detailed information of diagnostic findings, medications and their doses and dosage forms. Among 60 patients 36.7% were female patient and the rest 63.33% were male; both were in between 26-67 years. In this prescription the type of kidney disease was found like, Kidney failure, Kidney cancer, Kidney stone, Pyelonephritis, Glomerulonephritis, Acute renal failure, Chronic renal failure, Diabetic nephropathy, Nephrogenic diabetes insipidus, End stage renal disease (ESRD), Hypertensive nephropathy etc. The study shows that acute kidney failure was found to be most common (23.5%) and kidney cancer and End stage renal disease were found in a lowest number of patient (1.7%). All of the prescriptions contain multiple drugs. According to these prescriptions most commonly prescribed drugs were Furosemide (40%) and Amlodipine (40%) whereas Atenolol (15%) and Prednisolone (15%) were used in less number of prescription. The study was done on a limited scale, only 82 prescriptions were collected but additionally this can be done on a large scale to assess the scenario of kidney diseases of overall population of Bangladesh. Furthermore it is necessary to monitor the use of medication and its correlation with clinical outcome and quality of life to ensure the optimal use of health care resources.

DNA methylation and detection of cervical cancer and precancerous lesions using molecular methods.

Cervical cancer is the third most common cancer disease affecting the female population, and a key factor in the development of the disease is the human papillomavirus infection (HPV). The disease is also impacted by epigenetic changes such as DNA methylation, which causes activation or exclusion of certain genes. The aim of our review is to summarize and compare the most common molecular methods for detection of methylated promoter regions in biomarkers occurring in cervical carcinoma and also show the importance of connections of HR-HPV testing with methylation analysis in patients with cervical intraepithelial neoplasia. Insight into genetic and epigenetic alterations associated with cervical cancer development can offer opportunities for the molecular biomarkers that can be useful for screening, diagnosis, and also as new ways of treatment of cervical cancer precursor lesions.

Drug development for breast (BC), colorectal (CRC), and non-small cell lung cancers (NSCLC) over the past 34 years.

e17789 Background: The purpose of this study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. Methods: A pharmaceutical b...

多种化学因素对前列腺细胞连接蛋白Cx43的影响及对前列腺肿瘤治疗意义的研究进展

前列腺肿瘤(prostate cancer, PCa)作为常见的老年男性肿瘤疾病，发病率正在逐年上升，细胞连接蛋白(Connexon, Cx)的表达异常是其发生机制之一。研究表明前列腺肿瘤细胞较前列腺上皮表达Cx43明显降低，存在细胞间隙连接通讯(GJIC)缺陷，故Cx43表达缺陷可能在前列腺肿瘤发生发展过程中发挥一定作用。研究发现茶多酚类物质，含硒类物质、激素类物质、维生素类、生物碱类等多种化学物质都对前列腺肿瘤细胞Cx43的表达有影响，进而影响前列腺肿瘤发展状况，故本文将对多种化学因素对前列腺肿瘤细胞连接蛋白Cx43的影响及治疗意义作一综述。 Prostate cancer is a common cancer disease within older male populations and its incidence rate increased year by year. The abnormal exception of connexon is one of its pathogenesis. Researches show that Cx43 expression in prostate cancer was effectively lower compared with prostate epi-thelial, what’s more, there existed a gap junctional intercellular communication defects in prostate cancer. So, Cx43 expression defects may significantly affect the prostate cancer process. Researches also show that tea polyphenols substances, selenium substances, hormone-like substances, vitamins, alkaloids, and other chemical substances are also have different levels of effects on the expression of Cx43 in prostate tumor cells. Therefore, they also influenced the development of prostate cancer. So, the following article will mainly state the effecting of variety chemical factors on Cx43 in prostate cancer cells and therapeutic implications.

Regulative Effect of Nampt on Tumor Progression and Cell Viability in Human Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer disease. Here we examined Nampt expression in patients with CRC and the effect of Nampt on cell viability in CRC cells. Nampt protein was overexpressed in colorectal adenoma as well as colorectal carcinoma. The immunoreactive staining of Nampt was negative in the adjacent normal colorectal tissue, weak in colorectal adenoma, and strong in colorectal carcinoma, which may represent tumor progression. Further evaluation of clinical data showed that Nampt expression was not correlated with the clinicopathological characteristics of CRC. Additionally, our in vitro studies demonstrated that Nampt promotes CRC cell viability, whereas the Nampt inhibitor FK866 suppressed CRC cell viability, which was in concordance with the previous studies in other cancer cells. Treatment with Nampt-siRNA reduced the Nampt protein expression resulting in the inhibition of the cell viability of HCT116 and Caco2. Thus, the involvement of Nampt in cell growth indicates that Nampt may play an important role in colorectal tumorigenesis. As a consequence, our results suggest that Nampt may be considered as a progression marker of colorectal tumor and a potentially therapeutic target for the treatment of CRC.

Socioeconomic status and concomitant diseases in patients with prostate cancer.

e16076 Background: Prostate cancer remained the most common cancer disease in Sweden. The prognosis is relatively good (five year survival 87%, 2011). Today there is an ongoing discussion about how socioeconomic status (SES) and concomitant diseases could influence the outcome. This study aims to evaluate the potential association between tumor stage (TNM), concomitant diseases, SES and outcome among prostate cancer patients in a specific region of Sweden. Methods: This cross-sectional, retrospective registry study included 3.942 men diagnosed with prostate cancer (ICD-O-2: C61.9) during 2009-2010 in the region Stockholm-Gotland. The cohort was identified in the Swedish Cancer Registry. Data regarding other diagnoses, dispensed and administered drugs, surgery and radiotherapy and other diseases was collected through record linkage with other population based registries. Socioeconomic data on education, income and civil status was also used. Results: During the study period, 181 diagnosed patients died. Fo...

SOCIALINIO DARBUOTOJO VEIKLOS POREIKIS SPRENDŽIANT MOTERŲ, SERGANČIŲ KRŪTIES VĖŽIU, SOCIALINES – PSICHOLOGINES PROBLEMAS

Krūties vėžys – viena dažniausiai pasitaikančių moterų onkologinių ligų. Kasmet sergamumas šia liga vis didėja. Pastebėta, kad šia liga serga vis jaunesnės moterys. Pastaraisiais metais Lietuvoje kasmet nustatoma apie 1300 naujų krūties vėžio atvejų. Sirgdamos šia liga, moterys susiduria su įvairiomis psichologinėmis ir socialinėmis problemomis. Dėl gydymo dažnai pasikeičia moters išvaizda, moteris atsiriboja nuo aplinkinių, artimųjų, nuolatos jaučia baimę ir nerimą dėl savęs, artimųjų ir ateities, taip pat nuolat patiria stresą, kurį sukelia gydymo pasekmės ir kiti stresoriai. Todėl labai svarbu išsiaiškinti, koks yra socialinio darbuotojo veiklos poreikis sergančioms moterims, kad būtų galima padėti joms sumažinti keliamas socialines – psichologines problemas. Apklaustos moterys teigė, kad socialinis darbuotojas joms būtų labai naudingas, kadangi esant stacionarioje gydymo įstaigoje dažnai atsiranda įvairių klausimų ne tik joms, bet ir jų artimiesiems. Apklaustos moterys išreiškė konsultacijų poreikį joms ir jų artimiesiems apie reabilitacinėms paslaugoms priklausančias sanatorijas, socialinės paramos išmokas, taip pat jos norėtų, kad socialinis darbuotojas konsultuotų apie savipagalbos grupes. Apklaustos moterys norėtų, kad socialinis darbuotojas suteiktų joms daugiau informacijos apie kompensacinę techniką ( specialias liemenėles) ir jos gavimą, moterų, sergančių krūties vėžiu, teises ir jas ginančius įstatymus.

Common Fusion Transcripts Identified in Colorectal Cancer Cell Lines by High-Throughput RNA Sequencing

Colorectal cancer (CRC) is the third most common cancer disease in the Western world, and about 40% of the patients die from this disease. The cancer cells are commonly genetically unstable, but only a few low-frequency recurrent fusion genes have so far been reported for this disease. In this study, we present a thorough search for novel fusion transcripts in CRC using high-throughput RNA sequencing. From altogether 220 million paired-end sequence reads from seven CRC cell lines, we identified 3391 candidate fused transcripts. By stringent requirements, we nominated 11 candidate fusion transcripts for further experimental validation, of which 10 were positive by reverse transcription-polymerase chain reaction and Sanger sequencing. Six were intrachromosomal fusion transcripts, and interestingly, three of these, AKAP13-PDE8A, COMMD10-AP3S1, and CTB-35F21.1-PSD2, were present in, respectively, 18, 18, and 20 of 21 analyzed cell lines and in, respectively, 18, 61, and 48 (17%-58%) of 106 primary cancer tissues. These three fusion transcripts were also detected in 2 to 4 of 14 normal colonic mucosa samples (14%–28%). Whole-genome sequencing identified a specific genomic breakpoint in COMMD10-AP3S1 and further indicates that both the COMMD10-AP3S1 and AKAP13-PDE8A fusion transcripts are due to genomic duplications in specific cell lines. In conclusion, we have identified AKAP13-PDE8A, COMMD10-AP3S1, and CTB-35F21.1-PSD2 as novel intrachromosomal fusion transcripts and the most highly recurring chimeric transcripts described for CRC to date. The functional and clinical relevance of these chimeric RNA molecules remains to be elucidated.

Skin cancer prevention

Prevention signifies the avoidance of diseases. It also includes the early detection of diseases and taking measures to avoid worsening of an existing disease. Prevention is divided into primary, secondary and tertiary prevention. The prevention of skin cancer is particularly important due to the rising incidence of skin cancer in recent years. In Germany, 195.000 new cases of skin cancer, including non melanoma skin cancer and melanoma are occurring. Therefore, skin cancer is among the most common cancer diseases. Primary prevention comprises the reduction of skin cancer risk behavior, including education about the danger of UV exposure and the right way of dealing with natural and artificial UV radiation. The implementation of a systematic skin cancer screening in Germany contributes to secondary prevention. First data from the initial project in Schleswig-Holstein, Germany's most northern state, indicate for the first time that the incidence and mortality of melanoma can be reduced by secondary prevention. For tertiary prevention, the national associations recommend a risk-adapted, evidence-based follow-up for all types of skin cancer. From the perspectives of the payers and from the patients, prevention is assessed positively. Prevention can contribute to a reduction of disease burden.

An automatic computer-aided diagnosis system for liver tumours on computed tomography images

Liver cancer, one of the more common cancer diseases that cause a large number of deaths every year, can be reduced by early detection and diagnosis. Computer-Aided Diagnosis (CAD) can play a key role in the early detection and diagnosis of liver cancer. This paper develops a novel computer-aided diagnosis system focussing on the discriminating power of statistical texture descriptors in characterizing hepatocellular (malignant) from hemangioma (benign) liver tumours. The CAD system consists of three stages: (i) automatic tumour segmentation, (ii) texture feature extraction and (iii) tumour characterization using a classifier. Specifically, four features sets, the original gray level; co-occurrence of gray level; wavelet coefficient statistics and contourlet coefficient statistics are extracted from the tumour region of interest. A probabilistic neural network classifier is used to investigate the ability of each feature set in differentiating malignant from benign tissues. The performance of the CAD system evaluated using a database of images indicates that the highest accuracy achieved is 96.7% and the highest sensitivity and specificity are 97.3% and 96%, respectively that had been obtained with the contourlet coefficient co-occurrence features. The experimental results suggest that the developed CAD system has great potential and promise in the automatic diagnosis of both benign and malignant tumours of liver.

Abstract A28: Role of PDGF signaling during the progression of breast ductal carcinoma in situ to invasive carcinoma

Abstract Breast cancer is one of the most common cancer diseases; in Sweden over 7000 women are diagnosed yearly and 1500 die from the disease. About 20 % of newly diagnosed breast cancers are ductal carcinoma in situ (DCIS), an early stage of breast cancer. The majority of DCIS will never become malignant but 15-20 % will proceed to invasive carcinoma and/or metastasize. Predicative markers for invasiveness are highly needed to understand which tumors will recur and to prevent over treatment. Tumor characteristics are determined by interactions between malignant cells and the microenvironment. Cancer associated fibroblasts (CAFs) are a major component of the tumor microenvironment and one important regulator of their phenotype are the PDGFs, which signal through the PDGFα and β receptors (PDGFRs). Our previous studies in invasive breast carcinoma have shown that high stromal PDGFβR expression is associated with shorter survival, particularly in pre-menopausal women. The aim of this study is to investigate the potential prognostic significance of stromal PDGFRs in the transition of breast DCIS to invasive carcinoma. We found that both PDGFRs are highly expressed in normal breast stroma, whereas DCIS displays loss of periepithelial stromal PDGFαR. In contrast, patients with a high stromal PDGFβR expression in the DCIS lesion, showed a trend for a higher risk of local recurrence or general disease. These previously un-recognized potentially differential effects of stromal PDGFαR and PDGFβR signaling in breast cancer progression is presently being further explored in animal studies and in vitro experiments. Citation Format: Carina Strell, Janna Paulsson, Fredrik Wärnberg, Hemming Johansson, Karin Jirström, Per Hall, Arne Östman. Role of PDGF signaling during the progression of breast ductal carcinoma in situ to invasive carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A28.

Dying Without a Home: Understanding and Responding to Palliative and End-of-Life Care Needs of Homeless Patients (SA516)

1.Deepen our understanding of the complexities of treating homeless patients with life-limiting illness.2.Review the results of the study “Dying Without a Home: Understanding the Palliative and End-of-Life Care Needs of Homeless Patients.”3.Learn about a novel, comprehensive program to provide palliative and end-of-life care to homeless patients and lessons for providing this care in other settings. Patients experiencing homelessness suffer an excess of morbidity and mortality from life-limiting illness and may especially benefit from palliative care. Over the past 3 years, we have been building a comprehensive palliative care program at the Barbara McInnis House (BMH), part of the Boston Health Care for the Homeless Program (BCHCP). They provide high quality, culturally competent care to medically complex patients who do not meet criteria for acute hospitalization but are too ill to be on the streets. In this session, we will review data from a large, recently completed study on mortality among homeless patients conducted by Travis Baggett, MD MPH, that outlines the epidemic of deaths related to substance abuse and the heavy toll of common palliative care diseases, cancer, and heart and liver disease. There is a dearth of research on the palliative care needs of this population and how to best address them. However, what research has been done has revealed important themes that are novel in the palliative care literature and highlight some of the differences between the homeless and housed patients. We will review this research and present the findings of a study we conducted of 20 hospice eligible patients cared for at the BMH exploring their symptom burden, attitudes, and experiences with end-of-life care. We will explain the model of care used at BHCHP and the palliative and end-of-life care model we are developing at the BMH. Using available data and the combined clinical expertise of the Palliative Care Service at Massachusetts General Hospital and BHCHP, we are creating a focused curriculum, clinical protocols, and a model of care for homeless patients. We will present a patient case to illustrate the complexity of providing care to this population, the findings of our research, and the model of care we have developed.

Chirurgie des Pankreaskarzinoms

Ductal pancreatic carcinomas are currently the fourth most common fatal cancer disease with a survival rate of less than 5 % when all stages are considered. Other malignant pancreatic tumours have markedly better prognoses. Even after complete resection and adjuvant chemotherapy, the 5-year survival rate amounts to merely 20 - 25%. Besides a high resistance to chemotherapy and early lympho- and haematogenic metastases, the reason for this is often tumour extension beyond the medial and dorsal resection margins. In standardised pathological examinations cancer cells can be detected in the resection margins in about 75 % of the cases, which reflect the aggressive and infiltrative tumour growth and probably explains the high rate of local recurrence. Standard operations for curative tumour resection are the pylorus-preserving pancreatoduodenectomy (PPPD) and the left pancreatic resection with splenectomy in cases of pancreas tail tumours. In high-volume centres the mortality can be reduced to under 3 % and the long-term survival improved with an increase of the resection rate. Considering surgical complications, pancreatic fistulas with a prevalence of up to 10 % play a decisive role. The technique of the pancreatic anastomosis as well as closure of the pancreatic tail thus represents major surgical challenges. In view of the high recurrence rate of pancreatic carcinomas, extended surgical procedures have been examined in numerous studies. Although infiltration of the portal vein is not a contraindication for curative resection with vascular reconstruction which gives comparable survival rates, a radical, extended lymphadenectomy does not seem reasonable on the basis the available data. In selected, individual cases, patients may benefit from neoadjuvant radiochemotherapy to down-stage an unresectable tumour with subsequent tumour resection, a metastasis resection, or a resection of a local recurrence. An R0 resection and tumour-free lymph nodes (N0 stage) are the two factors that can provide the best prognosis for the patient with a median survival of 2 years and a good quality of life. Pancreas surgery is being increasingly oriented to the evidence-based data from randomised, controlled studies. In order to achieve a further and urgently needed improvement in treatment results, one should consider, if possible, all suitable patients for enrolment in current clinical studies on neoadjuvant, surgical, or adjuvant therapy.

Characterization of a human breast cancer cell line, MCF-7/RU58R-1, resistant to the pure antiestrogen RU 58,668

Breast cancer is the most common cancer disease in women in the western world. Tamoxifen has been the standard first line endocrine therapy for patients with estrogen receptor (ER) positive tumors. Unfortunately, almost all patients with advanced disease develop tamoxifen resistance. This has lead to a search for new potent antiestrogens. One of the new compounds under development is the pure antiestrogen RU 58,668. To study the mechanisms behind acquired resistance to RU 58,668, the RU 58,668-resistant cell line MCF-7/RU58(R)-1 (RU58(R)-1) was developed. The RU58(R)-1 cell line was responsive to tamoxifen, but cross-resistant to ICI 182,780 and the estrogen-sensitivity was reduced compared to the parental MCF-7 cell line. The protein levels of ERalpha, IGF-I Receptor (IGF-IR) and Bcl-2 were severely reduced, when RU58(R)-1 cells were cultured with RU 58,668 and the expression of progesterone receptor (PR) was lost. The ERalpha level increased upon withdrawal of RU 58,668 and the ERalpha protein was destabilized by RU 58,668 in both cell lines. Regulation of most of the investigated estrogen-sensitive mRNAs was found to be normal in the resistant cells. The protein levels of IGF-IR, Bcl-2 and the IGF Binding Protein 2 (IGFBP2) reverted towards MCF-7 levels upon RU 58,668 withdrawal, but the resistant phenotype was maintained. Thus, it appears as acquired resistance to RU 58,668 is not a result of loss of the ERalpha expression or function and we suggest that in the presence of RU 58,668, the RU58(R)-1 cell line probably uses other mitogenic pathways than the ERalpha pathway for growth and survival.

Inflammation: Mediators of Inflammation

In response to pathogens, injury or irritation, inflammation is a natural biological mechanism. The inflammation process is a difficult immune response that can be characterised as the synchronous activation of pro-inflammatory cytokines. Inflammation seems to be significantly correlated with various types of diseases, such as arthritis, allergy, atherosclerosis and cancer. Some intermittent events, including redness, swelling, heat, and pain, often progressing to exudation and loss of function, typically describe inflammation. Some inflammatory cytokines that are important chemical substances found in the tissues of the body, including prostaglandins, leukotrienes, prostacyclin, lymphocytes, and chemokines such as interferon-alpha (IFN-α), IFN-γ, are involved in the inflammation phase. Vegetables and fruit-derived formulations have been used to treat inflammatory conditions and their associated disorders. Evidence shows that fruits like grapes, watermelon, orange and vegetable-rich diets like Allium cepa, Momordica charantia, Raphanus sativus etc. are beneficial against common chronic diseases, cancer, obesity and cardiovascular diseases. In addition, these fruits and vegetables provide vitamins, minerals and fibre in our diet. Anti-inflammatory compounds in onions help to lessen the clinical symptoms associated with conditions like osteoarthritis and rheumatoid arthritis. Due to the presence of various phytochemicals in bitter melon, it is used in inflammation in bones and joints, inflammation in cancer and cardiovascular as well as neurodegenerative diseases and haemorrhoids. Lycopene in tomato also acts on cytokine channels in human adipose tissue, and inhibit the level of inflammatory biomarkers. This article focuses on such healthy foods and vegetables that have the capability to treat inflammatory disorders. From this we can conclude that fruits and vegetables are promising in limiting the inflammation.