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Sample records for cancer pancreatic cancer

  1. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  2. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  3. PANCREATIC CANCER

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  4. Epidemiology of pancreatic cancer

    OpenAIRE

    Ilic, Milena; Ilic, Irena

    2016-01-01

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied ...

  5. Diabetes and pancreatic cancer

    OpenAIRE

    Christine Hsu; Muhammad Wasif Saif

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Risk factors for pancreatic cancer are smoking, family history, chronic pancreatitis, and diabetes. There is controversy with regards to the causal relationship between diabetes and pancreatic cancer because many patients with pancreatic cancer have new onset diabetes. Abstracts presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting highlighted and supported the positive association ...

  6. Inherited pancreatic cancer syndromes.

    Science.gov (United States)

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  7. Obesity, pancreatitis, and pancreatic cancer.

    Science.gov (United States)

    Gumbs, Andrew A

    2008-09-01

    The only universally accepted risk factors for the development of pancreatic cancer are a positive family history or a history of smoking. Although the contribution of pancreatitis to pancreatic carcinogenesis has been debated for decades in the epidemiology literature, the actual mechanism is still unclear. With the rising epidemic of obesity, scientists have begun to focus on the contribution of chronic inflammatory state of morbidly obese patients in an effort to better understand the contribution of inflammation to the comorbidities of obesity. Notably, population studies are beginning to show that one of the most serious potential comorbidities of obesity is an increased lifetime risk of developing cancer. In this article, the current literature that exists supporting this Chronic Inflammatory Hypothesis as it pertains to obesity and pancreatic carcinogenesis is reviewed. To date, studies have focused on interleukin-6, a cytokine known to play a role in obesity, chronic pancreatitis and pancreatic cancer. The anti-inflammatory adipocytokine, adiponectin, has also shown promise as a key player in this mechanism and has recently been found to be more specific than standard tumor markers in differentiating pancreatic cancer from chronic pancreatitis. If the pathogenesis of pancreatic cancer is related to hormone levels associated with obesity, such as adipocytokines, and cytokines associated with chronic inflammation, this could potentially lead to the development of new pancreatic cancer tumor markers and ultimately new therapies and methods of prevention.

  8. Diabetes and Pancreatic Cancer

    Science.gov (United States)

    Li, Donghui

    2011-01-01

    Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer. PMID:22162232

  9. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... risks of other cancers (or other health problems). Examples of genetic syndromes that can cause exocrine pancreatic cancer include: Hereditary breast and ovarian cancer syndrome , caused by mutations in the BRCA1 or BRCA2 genes Familial atypical ...

  10. Pancreatic Cancer Screening.

    Science.gov (United States)

    Das, Koushik K; Early, Dayna

    2017-09-06

    This review describes the rationale for pancreatic cancer screening, outlines groups that are at elevated risk for pancreatic cancer, and summarizes the relative risk in each setting. We also review the methods available for performing pancreatic cancer screening and the recommended screening intervals. Several genetic mutations have been identified that increase the risk for pancreatic cancer. Most are rare, however, and at-risk individuals are most often those with a strong family history of pancreatic cancer (with multiple family members affected) but no identifiable genetic mutation. Known genetic syndromes that increase the risk for pancreatic cancer include hereditary pancreatitis, familial atypical mole and multiple melanoma, Peutz-Jeghers syndrome, Lynch syndrome, BRCA mutations, and Li-Fraumeni syndrome. Genetic testing should be performed in conjunction with genetic counseling, and testing of an affected family member is preferred if possible.The goal of pancreatic cancer screening is to identify pancreatic cancer at an early, curable stage or, ideally, to identify precancerous lesions that can be resected to prevent the development of cancer. Imaging can be performed with either endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP). These techniques are generally considered to be complementary, although an advantage of EUS is that cysts or solid lesions can be sampled at the time of the procedure. Published results of small cohorts of high-risk patients in pancreatic cancer screening programs have demonstrated a high prevalence of small cystic lesions identified on EUS or MRCP, which often represent side-branch intraductal papillary mucinous neoplasms (IPMN). Knowledge of conditions and syndromes that increase pancreatic cancer risk allows one to identify those patients that may benefit from pancreatic cancer screening. As we gather evidence from large, international, multicenter cohorts of patients at high-risk for pancreatic

  11. Prevention of pancreatic cancer

    OpenAIRE

    Stefan Kuroczycki-Saniutycz; Agnieszka Grzeszczuk; Zbigniew Wojciech Zwierz; Paweł Kołodziejczyk; Jakub Szczesiul; Beata Zalewska-Szajda; Krystyna Ościłowicz; Napoleon Waszkiewicz; Krzysztof Zwierz; Sławomir Dariusz Szajda

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy...

  12. Chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

  13. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  14. Pancreatic Cancer Genetics

    OpenAIRE

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, ...

  15. Pancreatic Cancer Genetics.

    Science.gov (United States)

    Amundadottir, Laufey T

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS).

  16. Prevention of pancreatic cancer.

    Science.gov (United States)

    Kuroczycki-Saniutycz, Stefan; Grzeszczuk, Agnieszka; Zwierz, Zbigniew Wojciech; Kołodziejczyk, Paweł; Szczesiul, Jakub; Zalewska-Szajda, Beata; Ościłowicz, Krystyna; Waszkiewicz, Napoleon; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  17. Prevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Stefan Kuroczycki-Saniutycz

    2017-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  18. Tests for Pancreatic Cancer

    Science.gov (United States)

    ... from a gallstone, a tumor, or other disease). Tumor markers: Tumor markers are substances that can sometimes be found in the blood when a person has cancer. Two tumor markers may be helpful in pancreatic cancer: CA 19- ...

  19. Epidemiology of pancreatic cancer.

    Science.gov (United States)

    Ilic, Milena; Ilic, Irena

    2016-11-28

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11(th) most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease.

  20. Familial pancreatic cancer.

    Science.gov (United States)

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  1. Chronic Pancreatitis and Pancreatic Cancer Risk

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-01-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We...... computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity...... analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic...

  2. Updates on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ojas Vyas

    2014-05-01

    Full Text Available Pancreatic adenocarcinoma remains a therapeutic challenge. The American Cancer Society estimates that in 2014 about 46,420 people will be diagnosed with pancreatic cancer and about 39,590 people will die of pancreatic cancer in the United States [1]. The incidence of pancreatic carcinoma has markedly increased over the past several decades and it now ranks as the fourth leading cause of cancer-related death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. Although progress in the development of new cytotoxic and biological drugs for the treatment of pancreatic cancer continues, the outcome remains grim. Many organizations and associations have taken an effort to improve knowledge, understanding and outcome of patients with pancreatic cancer. Pancreas Club, since its founding in 1966, is aimed to promote the interchange of ideas between physicians and scientists focused on pancreas throughout the world in an informal “club” atmosphere. We attended the 48th Annual Meeting of Pancreas Club in Chicago and reviewed many interesting posters and oral presentations. Here we discuss a few selected abstracts.

  3. Obesity and Pancreatic Cancer.

    Science.gov (United States)

    Michaud, Dominique S

    Pancreatic cancer has few known risk factors, providing little in the way of prevention, and is the most rapidly fatal cancer with 7 % survival rate at 5 years. Obesity has surfaced as an important risk factor for pancreatic cancer as epidemiological studies with strong methodological designs have removed important biases and solidified the obesity associations. Moreover, studies indicate that obesity early in adulthood is strongly associated with future risk of pancreatic cancer and that abdominal obesity is an independent risk factor. There is increasing evidence suggesting long-standing diabetes type 2 and insulin resistance are important etiological factors of this disease, providing a strong mechanistic link to obesity. The challenge remains to determine whether intended weight loss in midlife will reduce risk of pancreatic cancer and to elucidate the complex underlying pathways directly involved with risk.

  4. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients......, and survival. The results are published annually. CONCLUSION: The Danish Pancreatic Cancer Database has registered data on 2,217 patients with microscopically verified ductal adenocarcinoma of the pancreas. The data have been obtained nationwide over a period of 4 years and 2 months. The completeness...

  5. Pancreatic groove cancer

    Science.gov (United States)

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  6. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  7. Pancreatic Cancer: A Review.

    Science.gov (United States)

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes.

  8. [The epidemiology of pancreatic cancer].

    Science.gov (United States)

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

  9. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... Treatment Research Pancreatic Cancer Treatment (PDQ®)–Patient Version General Information About Pancreatic Cancer Go to Health Professional ... lies between the stomach and the spine . Enlarge Anatomy of the pancreas. The pancreas has three areas: ...

  10. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    Science.gov (United States)

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  11. Brain Metastasis in Pancreatic Cancer

    OpenAIRE

    Marko Kornmann; Doris Henne-Bruns; Jan Scheele; Christian Rainer Wirtz; Thomas Kapapa; Johannes Lemke

    2013-01-01

    Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreat...

  12. Carbohydrate markers of pancreatic cancer.

    Science.gov (United States)

    Szajda, Sławomir Dariusz; Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zwierz, Krzysztof

    2011-01-01

    Pancreatic cancer is the fourth most common cause of death from cancer in the world and the sixth in Europe. Pancreatic cancer is more frequent in males than females. Worldwide, following diagnosis of pancreatic cancer, <2% of patients survive for 5 years, 8% survive for 2 years and <50% survive for only approx. 3 months. The biggest risk factor in pancreatic cancer is age, with a peak of morbidity at 65 years. Difficulty in the diagnosis of pancreatic cancer causes a delay in its detection. It is one of the most difficult cancers to diagnose and therefore to treat successfully. Additional detection of carbohydrate markers may offer a better diagnosis of pancreatic cancer. Carbohydrate markers of cancer may be produced by the cancer itself or by the body in response to cancer, whose presence in body fluids suggests the presence and growth of the cancer. The most widely used, and best-recognized, carbohydrate marker of pancreatic cancer is CA 19-9 [CA (carbohydrate antigen) 19-9]. However, the relatively non-specific nature of CA 19-9 limits its routine use in the early diagnosis of pancreatic cancer, but it may be useful in monitoring treatment of pancreatic cancer (e.g. the effectiveness of chemotherapy), as a complement to other diagnostic methods. Some other carbohydrate markers of pancreatic cancer may be considered, such as CEA (carcinoembryonic antigen), CA 50 and CA 242, and the mucins MUC1, MUC2 and MUC5AC, but enzymes involved in the processing of glycoconjugates could also be involved. Our preliminary research shows that the activity of lysosomal exoglycosidases, including HEX (N-acetyl-β-D-hexosaminidase), GAL (β-D-galactosidase), FUC (α-L-fucosidase) and MAN (α-D-mannosidase), in serum and urine may be used in the diagnosis of pancreatic cancer.

  13. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  14. Diet and Pancreatic Cancer Prevention.

    Science.gov (United States)

    Casari, Ilaria; Falasca, Marco

    2015-11-23

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  15. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  16. Vaginal metastasis of pancreatic cancer.

    Science.gov (United States)

    Benhayoune, Khadija; El Fatemi, Hinde; El Ghaouti, Meryem; Bannani, Abdelaziz; Melhouf, Abdelilah; Harmouch, Taoufik

    2015-01-01

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of symptoms from a vaginal metastasis.

  17. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  18. Screening for Pancreatic Cancer.

    Science.gov (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William

    2015-10-01

    Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.

  19. Immunoprevention of Pancreatic Cancer.

    Science.gov (United States)

    Rao, Chinthalapally; Mohammed, Altaf; Asch, Adam; Janakiram, Naveena

    2017-02-23

    Pancreatic cancer (PC) is a deadly disease, with a 5-year survival rate of 6% and has significantly changed over the decades. It is difficult to diagnose PC patients at early stages, as there are no early non-invasive biomarkers or early signs or symptoms of clinical diagnosis. The lack of effective treatment strategies is also a major concern for hindering survival rates. Vaccine-based treatments for several cancers are currently under intense investigation. Current vaccine testing for PC is usually performed in advanced stages of cancer, during which the patient's impaired immune responses improved to suppress the growing tumor. However, so far such strategies have had limited success and have not become mainstream therapies. Thus, early diagnosis is imperative for immunoprevention using vaccines. Developing vaccines towards non-self-antigens has been successful, whereas vaccines against self-antigens, without any adverse effects on normal cells, have been challenging. The development of new technologies to identify mutated antigens, post-translational alterations in proteins, and tumor-specific antigens is currently underway, with a view toward vaccine development. Combining vaccines with immunostimulators or non-toxic anticancer agents are promising for cancer prevention. Successful vaccination strategies for PC at different stages of tumor development and future challenges for immunoprevention are discussed in this review.

  20. Proteomics in Pancreatic Cancer Research

    Directory of Open Access Journals (Sweden)

    Ruihui Geng

    2011-01-01

    Full Text Available Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and deeply affects the life of people. Therefore, the earlier diagnosis and better treatments are urgently needed. In recent years, the proteomic technologies are well established and growing rapidly and have been widely applied in clinical applications, especially in pancreatic cancer research. In this paper, we attempt to discuss the development of current proteomic technologies and the application of proteomics to the field of pancreatic cancer research. This will explore the potential perspective in revealing pathogenesis, making the diagnosis earlier and treatment.

  1. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  2. Pancreatic cancer chemoradiotherapy.

    Science.gov (United States)

    Brunner, Thomas B; Seufferlein, Thomas

    2016-08-01

    Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.

  3. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos

    2007-01-01

    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  4. Neoadjuvant therapy in pancreatic cancer: review article.

    Science.gov (United States)

    Pross, Moritz; Wellner, Ulrich F; Honselmann, Kim C; Jung, Carlo; Deichmann, Steffen; Keck, Tobias; Bausch, Dirk

    2015-03-20

    Pancreatic cancer is still associated with a high mortality and morbidity for affected patients. To this date the role of neoadjuvant therapy in the standard treatment of pancreatic cancer remains elusive. The aim of our study was to review the latest results and current approaches in neoadjuvant therapy of pancreatic cancer. We performed a literature review for neoadjuvant therapy in pancreatic cancer. We divided the results into resectable disease and local advanced pancreatic cancer. Neoadjuvant therapy in pancreatic cancer is safe. But currently no standard guidelines exist in neoadjuvant approaches on pancreatic cancer. For local advanced pancreatic cancer the available data tends to show a positive effect on survival rates for neoadjuvant approaches. For resectable disease we found no benefit of neoadjuvant therapy. The negative or positive effects of neoadjuvant treatment in pancreatic cancer remain unclear for the lack of sufficient and prospective data.

  5. Role of bacterial infections in pancreatic cancer

    OpenAIRE

    Michaud, Dominique S.

    2013-01-01

    Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porp...

  6. Pancreatic cancer: yesterday, today and tomorrow.

    Science.gov (United States)

    Ansari, Daniel; Tingstedt, Bobby; Andersson, Bodil; Holmquist, Fredrik; Sturesson, Christian; Williamsson, Caroline; Sasor, Agata; Borg, David; Bauden, Monika; Andersson, Roland

    2016-08-01

    Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.

  7. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  8. Listeria Vaccines for Pancreatic Cancer

    Science.gov (United States)

    2013-10-01

    Immunol 20, 77 (Jan, 2013). 13. S. K. Biswas, C. E. Lewis, J Leukoc Biol 88, 877 (Nov, 2010). 14. L. J. Bayne et al., Cancer Cell 21, 822 (Jun 12, 2012...EMT and dissemination precede prancreatic tumor formation. Cell. 2012; 148:349. 14. Bayne , L.J., Beatty, G.L., Jhala, N., Clark, C.E., Rhim, A.D...immunity in pancreatic cancer. Cancer Cell. 2012; 21:822. 15. Vonderheide, RH, Bajor, DL, Bayne , LJ, and G.L. Beatty. CD40 immunotherapy for pancreatic

  9. Genetic abnormalities in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Zamboni Giuseppe

    2003-01-01

    Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.

  10. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  11. Obesity, Intrapancreatic Fatty Infiltration, and Pancreatic Cancer.

    Science.gov (United States)

    Wang, Hua; Maitra, Anirban; Wang, Huamin

    2015-08-01

    Obesity and intrapancreatic fatty infiltration are associated with increased risk of pancreatic cancer and its precursor lesions. The interplay among obesity, inflammation, and oncogenic Kras signaling promotes pancreatic tumorigenesis. Targeting the interaction between obesity-associated inflammation and Kras signaling may provide new strategies for prevention and therapy of pancreatic cancer. ©2015 American Association for Cancer Research.

  12. Pharmacogenomics Update in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Aditi Puri

    2014-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in United States. Despite advances in understandingcancer biology and therapeutics, this malignancy carries a grave prognosis with a poor overall survival rate. This is especiallytrue for patients with locally advanced and metastatic disease that are not amenable to surgical resection. Given advances inhuman genome sequencing and pharmacogenomics, we now better understand the complex genetic makeup of these tumorsand numerous gene mutations have been identified that could be potential targets for drug development. In this review, wediscuss two abstract (Abstracts #208 and #192 presented at the 2014 ASCO Gastrointestinal Cancers Symposium aboutpancreatic cancer genome sequencing and their implications for the future of this disease. We discuss what is known aboutthe genome of pancreatic tumors, including common mutations like KRAS, TP53 and SMAD4, as well as discovery ofadditional mutations. In particular, KRAS2 mutations in a subset of patients with pancreatic cancer are discussed. Whilelimited in size and clinical correlativity, these abstracts provide at least seven novel/targetable mutations and elucidatebiologic differences in tumors with wild type and mutant KRAS. These are important steps in understanding tumor biologyand genetic basis of pancreatic cancer to help develop targeted drug therapies in the fast approaching era of personalizedmedicine.

  13. Pancreatic cancer chemoprevention by phytochemicals.

    Science.gov (United States)

    Boreddy, Srinivas Reddy; Srivastava, Sanjay K

    2013-06-28

    Pancreatic cancer is fourth leading cause of cancer-related deaths in the United States of America. In spite of recent advances in the current therapeutic modalities such as surgery, radiation and chemotherapy patients, the average five year survival rate remains still less than 5%. Recently, compounds from natural sources receive ample of attention as anti-cancer agents. Many epidemiological studies published over the past few decades provide a strong correlation between consumption of vegetables, fruits or plant derived products and reduced incidence of cancer. The present review focuses on the potential antitumor effects of various natural products.

  14. Surgery for Pancreatic Cancer

    Science.gov (United States)

    ... is usually done through an endoscope (a long, flexible tube) while you are sedated. Often this is ... Select A Hope Lodge Close Please share your thoughts about your cancer.org website experience. If you ...

  15. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    Science.gov (United States)

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  16. Pancreatic Cancer Imaging: Which Method?

    Directory of Open Access Journals (Sweden)

    Santo E

    2004-07-01

    Full Text Available Pancreatic cancer is the 10th most common malignancy and the 4th largest cancer killer in adults. Surgery offers the only chance of curing these patients. Complete surgical resection is associated with a 5-year survival rate of between 20 and 30%. The challenge is how to best select those patients for curative surgery. Early studies demonstrated excellent sensitivity of EUS in detecting pancreatic tumors in comparison to CT. Similarly, EUS showed an 85-94% accuracy rate for T staging and 70-80% accuracy rate for N staging. Later studies report on substantially less TN staging accuracy for EUS. Possible explanations and the problem of vascular involvement assessment by EUS will be provided. Considering the role of EUS in M staging and a comparison between EUS, MRI, and positron emission tomography, scanning will be presented. A diagnostic algorithm for the evaluation of patients with a suspected pancreatic mass will be offered, stressing the pivotal role of EUS.

  17. Pain Management in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Michael Erdek

    2010-12-01

    Full Text Available A majority of pancreatic cancer patients present with pain at the time of diagnosis. Pain management can be challenging in light of the aggressive nature of this cancer. Apart from conventional pharmacotherapy, timely treatment with neurolytic celiac plexus block (NCPB has been shown to be of benefit. NCPB has demonstrated efficacious pain control in high quality studies with analgesic effects lasting one to two months. NCPB has also shown to decrease the requirements of narcotics, and thus decrease opioid related side effects. Another option for the control of moderate to severe pain is intrathecal therapy (IT. Delivery of analgesic medications intrathecally allows for lower dosages of medications and thus reduced toxicity. Both of the above mentioned interventional procedures have been shown to have low complication rates, and be safe and effective. Ultimately, comprehensive pancreatic cancer pain management necessitates understanding of pain mechanisms and delivery of sequential validated therapeutic interventions within a multidisciplinary patient care model.

  18. Somatostatin, somatostatin receptors, and pancreatic cancer.

    Science.gov (United States)

    Li, Min; Fisher, William E; Kim, Hee Joon; Wang, Xiaoping; Brunicardi, Charles F; Chen, Changyi; Yao, Qizhi

    2005-03-01

    Somatostatin may play an important role in the regulation of cancer growth including pancreatic cancer by interaction with somatostatin receptors (SSTRs) on the cell surface. Five SSTRs were cloned, and the function of these SSTRs is addressed in this review. SSTR-2, SSTR-5, and SSTR-1 are thought to play major roles in inhibiting pancreatic cancer growth both in vitro and in vivo. SSTR-3 may be involved in mediating apoptosis, but the role of SSTR-4 is not clear. In most pancreatic cancers, functional SSTRs are absent. Reintroduction of SSTR genes has been shown to inhibit pancreatic cancer growth in cell cultures and animal models.

  19. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... gene testing for hereditary pancreatitis is now available. Ataxia telangiectasia The team at Johns Hopkins discovered that inherited ... are known to cause the clinical syndrome of "ataxia telangiectasia," and 2-3% of people with familial pancreatic ...

  20. Hedgehog signaling and therapeutics in pancreatic cancer.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

  1. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  2. Epidemiology and prevention of pancreatic cancer.

    Science.gov (United States)

    Lowenfels, Albert B; Maisonneuve, Patrick

    2004-05-01

    Pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. In the United States it is the fourth most frequent cause of cancer mortality; in Japan it ranks as the fifth commonest cause of death from cancer. Smoking is the major known risk factor for pancreatic cancer, accounting for approximately 25-30% of all cases. Some of the time-dependent changes in the frequency of pancreatic cancer can be explained by smoking trends. Aggressive public health measures to control smoking would substantially reduce the burden of pancreatic cancer. Dietary factors are less important for pancreatic cancer than for other digestive tract tumors, but consumption of a diet with adequate quantities of fruits and vegetables, plus control of calories either by dietary measures or by exercise will help to prevent this lethal tumor. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors.

  3. Neoadjuvant strategies for pancreatic cancer

    OpenAIRE

    Polistina, Francesco; Di Natale, Giuseppe; Bonciarelli, Giorgio; Ambrosino, Giovanni; Frego, Mauro

    2014-01-01

    Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries, the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20% of all cases. Five years cumulative survival is less than 5% and rises to 25% for radically resected patients. About 40% has locally advanced in PC either borderline resectable (BRPC) or unresectable locally advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy (N...

  4. Future Directions in Pancreatic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    David Orchard-Webb

    2015-05-01

    Full Text Available Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics.

  5. Clusterin confers gmcitabine resistance in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Wang Yaoguang

    2011-05-01

    Full Text Available Abstract Objective To measure clusterin expression in pancreatic cancer tissues and cell lines and to evaluate whether clusterin confers resistance to gmcitabine in pancreatic cancer cells. Methods Immunohistochemistry for clusterin was performed on 50 primary pancreatic cancer tissues and 25 matched backgrounds, and clusterin expression in 5 pancreatic cancer cell lines was quantified by Western blot and PT-PCR. The correlation between clusterin expression level and gmcitabine IC50 in pancreatic cancer cell lines was evaluated. The effect of an antisense oligonucleotide (ASO against clusterin(OGX-011 on gmcitabine resistance was evaluated by MTT assays. Xenograft model was used to demonstrate tumor growth. Results Pancreatic cancer tissues expressed significantly higher levels of clusterin than did normal pancreatic tissues (P P In vivo systemic administration of AS clusterin and gmcitabine significantly decreased the s.c. BxPC-3 tumor volume compared with mismatch control ODN plus gmcitabine. Conclusion Our finding that clusterin expression was significantly higher in pancreatic cancer than in normal pancreatic tissues suggests that clusterin may confer gmcitabine resistance in pancreatic cancer cells.

  6. Diabetes, pancreatic cancer, and metformin therapy

    Directory of Open Access Journals (Sweden)

    Jun eGong

    2014-11-01

    Full Text Available Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1, and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.

  7. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  8. Living as a Pancreatic Cancer Survivor

    Science.gov (United States)

    ... pain Pancreatic cancer often causes weight loss and weakness from poor nutrition. These symptoms might be caused by treatment or by the cancer itself. A team of doctors and nutritionists can work with you ...

  9. What Is Pancreatic Cancer?

    Science.gov (United States)

    ... also called 5-HT ) or its precursor, 5-HTP. The treatment and outlook for pancreatic NETs depend ... known as precancers ). Because people are getting imaging tests such as CT scans more often than in ...

  10. Therapeutic Tools in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Christopher J Hoimes

    2009-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lower survival rate than other digestive tract tumors. It remains a therapeutic challenge with limited active agents. Honing our current understanding of markers of toxicity and response, and individualizing treatment with the prognostic and therapeutic tools available are important to make a worthy impact on a patient’s course. The authors summarize selected abstracts from the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, USA, January 15-17, 2009. The Symposium featured pancreatic cancer in 84 research abstracts, of which, seven are reviewed that focus on markers of toxicity: cytidine deaminase (Abstract #151 and haptogloin (Abstract #167 as markers of gemcitabine toxicity; markers of response: use of PET scan for prognosis (Abstract #157, and correlations with CA 19-9 to postchemo-radiation resectability (Abstract #215 and time to progression (Abstract #160; and individualized applications: characterizing the phenotypic similarities between a patient tumor and the direct xenograft (Abstract #154 and a report about the poor outcome of patients with ascites (Abstract #220. Validated clinical tools that can assist in managing patients through the narrow therapeutic window are needed.

  11. Pancreatic cancer: epidemiology and risk factors.

    Science.gov (United States)

    Krejs, Guenter J

    2010-01-01

    Ductal adenocarcinoma of the pancreas has an incidence of approximately 10 per 100,000 population per year. This number pertains to Europe, North America and parts of South America (Argentina). Men are more often afflicted than women (female:male ratio of about 1:1.5, though reports vary). There has been a very small but steady increase in the incidence over the last 50 years. Unfortunately, numbers for incidence and mortality are still practically identical for this cancer. The peak of incidence is between 60 and 80 years of age. In absolute numbers, there are 8,000 cases diagnosed annually in Germany, and 33,000 in the US. Pancreatic cancer at pancreatic cancer include high-fat diet, smoking, chronic pancreatitis, primary sclerosing cholangitis, hereditary pancreatitis, family history of pancreatic cancer and diabetes mellitus. In chronic pancreatitis, the risk for pancreatic cancer is increased 20-fold, in hereditary pancreatitis it is 60-fold higher than in the general population. In a kindred with 2 first-degree relatives with pancreatic cancer, the risk for pancreatic cancer for other members of that kindred is 7-fold higher.

  12. Current progress in immunotherapy for pancreatic cancer.

    Science.gov (United States)

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  13. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  14. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  15. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    Science.gov (United States)

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  16. Proton therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romaine; C; Nichols; Soon; Huh; Zuofeng; Li; Michael; Rutenberg

    2015-01-01

    Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.

  17. Pancreatic cancer stem cells: fact or fiction?

    Science.gov (United States)

    Bhagwandin, Vikash J; Shay, Jerry W

    2009-04-01

    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  18. Pancreatic cancer: from bench to bedside

    Science.gov (United States)

    Ma, Yaokai; Wu, Qing; Li, Xin; Gu, Xiaoqiang; Xu, Jiahua

    2016-01-01

    Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects.

  19. Roles of Fyn in pancreatic cancer metastasis.

    Science.gov (United States)

    Chen, Zhi-Yu; Cai, Lei; Bie, Ping; Wang, Shu-Guang; Jiang, Yan; Dong, Jia-Hong; Li, Xiao-Wu

    2010-02-01

    Src family kinases have been suggested to be associated with the metastasis of tumors, but their related mechanisms remain unclear. The aims of the present study were to assess the possible mechanisms by which the inhibition of Fyn activation regulates pancreatic cancer metastasis. We examined the expressions of Fyn in human pancreatic cancer tissues by immunohistochemistry and systematically investigated the relationship between Fyn expression and pancreatic cancer metastasis. A nude mouse xenograft model induced by BxPC3 cells with or without the inhibition of Fyn activation was used to explore the effect of the inhibition of Fyn on metastasis in vivo. Methyl thiazolyl tetrazolium and terminal deoxynucleotidyl transferase-labeling assays were used to examine the effect of the inhibition of Fyn on the cell proliferation of BxPC3 pancreatic cancer cells in vitro. Reverse transcription polymerase chain reaction and Western blot analysis were performed to explore the possible mechanism of Fyn-induced metastasis. We found that the upregulation of Fyn expression was correlated with human pancreatic cancer metastasis. In BxPC3 pancreatic cancer cells, the inhibition of Fyn activation by kinase-dead Fyn transfection decreased liver metastasis in nude mice. Further analyses showed that Fyn activity modulated pancreatic cell metastasis through the regulation of proliferation and apoptosis. Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis.

  20. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira-Cunha, Melissa, E-mail: melissacunha@doctors.org.uk [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Newman, William G. [Genetic Medicine, MAHSC, University of Manchester, St Mary' s Hospital, Oxford Road, Manchester, M13 9WL (United Kingdom); Siriwardena, Ajith K. [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom)

    2011-03-24

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

  1. Protein Ubiquitylation in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Thomas Bonacci

    2010-01-01

    Full Text Available Pancreatic cancer is one of the worst, as almost 100% of patients will die within 5 years after diagnosis. The tumors are characterized by an early, invasive, and metastatic phenotype, and extreme resistance to all known anticancer therapies. Therefore, there is an urgent need to develop new investigative strategies in order to identify new molecular targets and, possibly, new drugs to fight this disease efficiently. Whereas it has been known for more than 3 decades now, ubiquitylation is a post-translational modification of protein that only recently emerged as a major regulator of many biological functions, dependent and independent on the proteasome, whose failure is involved in many human diseases, including cancer. Indeed, despite its role in promoting protein degradation through the proteasome, ubiquitylation is now known to regulate diverse cellular processes, such as membrane protein endocytosis and intracellular trafficking, assembly of protein complexes, gene transcription, and activation or inactivation of enzymes. Taking into account that ubiquitylation machinery is a three-step process involving hundreds of proteins, which is countered by numerous ubiquitin hydrolases, and that the function of ubiquitylation relies on the recognition of the ubiquitin signals by hundreds of proteins containing a ubiquitin binding domain (including the proteasome, the number of possible therapeutic targets is exceptionally vast and will need to be explored carefully for each disease. In the case of pancreatic cancer, the study and the identification of specific alteration(s in protein ubiquitylation may help to explain its severity and may furnish more specific targets for more efficient therapies.

  2. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  3. Acute pancreatitis in patients with pancreatic cancer

    Science.gov (United States)

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  4. Endoscopic management of pain in pancreatic cancer.

    Science.gov (United States)

    Mekaroonkamol, Parit; Willingham, Field F; Chawla, Saurabh

    2015-01-31

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and one of the leading causes of cancer mortality in the United States. Due to its aggressive behavior and lack of effective therapies, palliation plays a critical role in the management of the disease. Most patients with pancreatic cancer suffer from severe pain, which adversely predicts prognosis and significantly impacts the quality of life. Therefore pain management plays a central role in palliation. Non-steroidal anti-inflammatory drugs and opioid agents are often first line medications in pain management, but they do not target the underlying pathophysiology of pain and their use is limited by adverse effects and dependence. The proposed mechanisms of pain development in pancreatic cancer include neurogenic inflammation and ductal hypertension which may be targeted by endoscopic therapies. Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and pancreatic duct stent placement are the two primary endoscopic modalities for palliative management in pancreatic cancer patients with refractory pain.  Other endoscopic treatments such as biliary stent placement and enteral stent placement for biliary and duodenal obstruction may also help palliate pain in addition to their role in decompression. This article reviews the existing evidence for these endoscopic interventions for pain management in pancreatic cancer.

  5. Management of borderline resectable pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Amit; Mahipal; Jessica; Frakes; Sarah; Hoffe; Richard; Kim

    2015-01-01

    Pancreatic cancer is the fourth most common cause of cancer death in the United States. Surgery remains the only curative option; however only 20% of the patients have resectable disease at the time of initialpresentation. The definition of borderline resectable pancreatic cancer is not uniform but generally denotes to regional vessel involvement that makes it unlikely to have negative surgical margins. The accurate staging of pancreatic cancer requires triple phase computed tomography or magnetic resonance imaging of the pancreas. Management of patients with borderline resectable pancreatic cancer remains unclear. The data for treatment of these patients is primarily derived from retrospective single institution experience. The prospective trials have been plagued by small numbers and poor accrual. Neoadjuvant therapy is recommended and typically consists of chemotherapy and radiation therapy. The chemotherapeutic regimens continue to evolve along with type and dose of radiation therapy. Gemcitabine or 5-fluorouracil based chemotherapeutic combinations are administered. The type and dose of radiation vary among different institutions. With neoadjuvant treatment, approximately 50% of the patients are able to undergo surgical resections with negative margins obtained in greater than 80% of the patients. Newer trials are attempting to standardize the definition of borderline resectable pancreatic cancer and treatment regimens. In this review, we outline the definition, imaging requirements and management of patients with borderline resectable pancreatic cancer.

  6. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  7. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or

  8. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence

  9. Phase 1 Trials in Pancreatic Cancer

    OpenAIRE

    Esther Yu; Muhammad Wasif Saif; Kathryn Huber

    2014-01-01

    Despite many clinical trials over the last two decades since the approval of gemcitabine, the survival of patients with pancreatic cancer has improved by a few only months. This disappointing reality underlines an urgent need to develop more effective drugs or better combinations. A variety of phase I trials were presented at the annual meeting of ASCO 2014 focusing on locally advanced and metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116, #4123, #4026, #4138).

  10. Phase 1 Trials in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Esther Yu

    2014-07-01

    Full Text Available Despite many clinical trials over the last two decades since the approval of gemcitabine, the survival of patients with pancreatic cancer has improved by a few only months. This disappointing reality underlines an urgent need to develop more effective drugs or better combinations. A variety of phase I trials were presented at the annual meeting of ASCO 2014 focusing on locally advanced and metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116, #4123, #4026, #4138.

  11. Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

    Science.gov (United States)

    2016-05-19

    Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  12. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  13. Increased pancreatic cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

    2016-01-01

    BACKGROUND: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. METHODS: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer...... patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). RESULTS: Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated...... with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

  14. Diabetes Type 2 and Pancreatic Cancer: A History Unfolding

    OpenAIRE

    Andre Souza; Khawaja Irfan; Faisal Masud; Muhammad Wasif Saif

    2016-01-01

    Pancreatic Cancer is the fourth cause of cancer-related deaths in the United States. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent literature suggests that diabetes mellitus type 2 is a risk factor, a manifestation and a prognostic factor for pancreatic cancer. This article is intended to clarify the evidence about diabetes as a risk factor for pancreatic cancer.

  15. Diabetes Type 2 and Pancreatic Cancer: A History Unfolding

    Directory of Open Access Journals (Sweden)

    Andre De Souza

    2016-03-01

    Full Text Available Pancreatic Cancer is the fourth cause of cancer-related deaths in the United States. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent literature suggests that diabetes mellitus type 2 is a risk factor, a manifestation and a prognostic factor for pancreatic cancer. This article is intended to clarify the evidence about diabetes as a risk factor for pancreatic cancer.

  16. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  17. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer.

    Science.gov (United States)

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar

    2016-11-01

    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  18. Multimodality Treatment in Pancreatic and Periampullary Cancer

    NARCIS (Netherlands)

    M.J.M. Morak (Marjolein)

    2015-01-01

    markdownabstract__Abstract__ Pancreatic cancer is the eight most common form of cancer in Europe with 96.000 new cases yearly. This incidence closely matches the mortality rate, thus revealing the aggressive behaviour of this tumour. Five-year survival after diagnosis is only 5% with a median overa

  19. Treatment of Pancreatic Cancer with Pharmacological Ascorbate.

    Science.gov (United States)

    Cieslak, John A; Cullen, Joseph J

    2015-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.

  20. [CORRELATION BETWEEN OBESITY AND PANCREATIC CANCER].

    Science.gov (United States)

    Pin, Maja; Štimac, Davor

    2015-01-01

    Pancreatic cancer is an aggressive tumor with a very poor prognosis, lack of early diagnostic symptoms and highly resistant to therapy. Its incidence is approximately equal to the mortality rate. Even though in recent years progress has been made in defining the morphological and key genetic changes, it is still unclear which factors trigger its occurrence. Some risk factors are age, gender and race, genetic susceptibility, dietary factors, fever, chronic pancreatitis, diabetes and physical inactivity. Studies have shown that an increase in BMI consequently leads to an increased risk of malignancies, including pancreatic cancer. Research based on adipokines and their role in obesity and the occurrence of pancreatic cancer are the potential for a possible future therapeutic interventions.

  1. Cancer surveillance of patients from familial pancreatic cancer kindreds.

    Science.gov (United States)

    Brentnall, T A

    2000-05-01

    The family history can be used to determine which family members warrant surveillance and when to start it. Surveillance should be started at least 1 decade before the earliest age of pancreatic cancer in the family. EUS is the basic, least-invasive surveillance tool; however, findings are similar to those seen in chronic pancreatitis. All patients who have a positive EUS or who have symptoms warrant ERCP. Changes on ERCP of ductal stricturing and clubbed or saccular side branches are suggestive of patients who may need pancreatectomy in the setting of hereditary pancreatic cancer. The goal for surveillance of familial pancreatic cancer patients is to diagnose them before the development of cancer, when they have dysplasia or carcinoma in situ, and to perform a complete pancreatectomy. Timing is crucial for determining when a patient warrants surgery; if performed too early, the patient is put at risk for the morbidity and mortality of a total pancreatectomy, which is not inconsequential. If the patient survives the operation, he or she is often left a brittle diabetic. The alternative of diagnosing too late is more worrisome because the patient dies of pancreatic cancer. An essential ingredient to a good patient outcome is a team approach to these patients, using gastroenterologists, surgeons, and pathologists who have expertise and interest in pancreatic disease.

  2. [Differential diagnosis of pancreatic head cancer].

    Science.gov (United States)

    Kubyshkin, V A; Vishnevskiĭ, V A; Aĭrapetian, A T; Karmazanovskiĭ, G G; Kuntsevich, G I; Starkov, Iu G

    2000-01-01

    The results of clinical, instrumental and laboratory examinations were analyzed for 99 patients. 59 of them had pancreatic head cancer, 40--chronic pseudotumorous pancreatitis. The importance of complex ultrasonic diagnosis in detection of pancreatic diseases (98%), in true diagnosis of unresectable tumors (96.7%), and also in determination of bile ducts lesion level in obstructive jaundice is shown. It was revealed that spiral computed tomography (SCT) had an advantage over computed tomography in diagnosis of pancreatic tumors and in assessment of their resectability. Sensitivity of combined use of US, SCT and tumor marker CA 19-9 in pancreatic cancer diagnosis increases to 95.2%. High diagnostic value of laparoscopy with laparoscopic ultrasonic examination as a method of final assessment of tumor resectability is shown.

  3. Metformin induces apoptosis of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To assess the role and mechanism of mefformin in inducing apoptosis of pancreatic cancer cells. METHODS: The human pancreatic cancer cell lines ASPC-1, BxPc-3, PANC-1 and SW1990 were exposed to mefformin. The inhibition of cell proliferation and colony formation via apoptosis induction and S phase arrest in pancreatic cancer cell lines of mefformin was tested.RESULTS: In each pancreatic cancer cell line tested, metformin inhibited cell proliferation in a dose dependent manner in MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays). Flow cytometric analysis showed that metformin reduced the number of cells in G1 and increased the percentage of cells in S phase as well as the apoptotic fraction. Enzymelinked immunosorbent assay (EUSA) showed that metformin induced apaptosis in all pancreatic cancer cell lines. In Western blot studies, metformin induced oly-ADP-ribose polymerase(PARP) cleavage (an indicator of aspase activation) in all pancreatic cancer cell lines. The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells. We also observed that metformin treatment ramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.CONCLUSION: Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP leavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metforrnin-induced apoptosis in pancreatic cell lines.

  4. Microbiota, oral microbiome, and pancreatic cancer.

    Science.gov (United States)

    Michaud, Dominique S; Izard, Jacques

    2014-01-01

    Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease.

  5. Increased pancreatic cancer risk following radiotherapy for testicular cancer.

    Science.gov (United States)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

    2016-09-27

    Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

  6. Neoadjuvant strategies for pancreatic cancer.

    Science.gov (United States)

    Polistina, Francesco; Di Natale, Giuseppe; Bonciarelli, Giorgio; Ambrosino, Giovanni; Frego, Mauro

    2014-07-28

    Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries, the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20% of all cases. Five years cumulative survival is less than 5% and rises to 25% for radically resected patients. About 40% has locally advanced in PC either borderline resectable (BRPC) or unresectable locally advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy (NT) has increasingly became a valid treatment option. The aim of NT is to reach local control of disease but, also, it is recognized to convert about 40% of LAPC patients to R0 resectability, thus providing a significant improvement of prognosis for responding patients. Once R0 resection is achieved, survival is comparable to that of early stage PCs treated by upfront surgery. Thus it is crucial to look for a proper patient selection. Neoadjuvant strategies are multiples and include neoadjuvant chemotherapy (nCT), and the association of nCT with radiotherapy (nCRT) given as either a combination of a radio sensitizing drug as gemcitabine or capecitabine or and concomitant irradiation or as upfront nCT followed by nRT associated to a radio sensitizing drug. This latter seem to be most promising as it may select patients who do not go on disease progression during initial treatment and seem to have a better prognosis. The clinical relevance of nCRT may be enhanced by the application of higher active protocols as FOLFIRINOX.

  7. Neoadjuvant strategies for pancreatic cancer

    Science.gov (United States)

    Polistina, Francesco; Di Natale, Giuseppe; Bonciarelli, Giorgio; Ambrosino, Giovanni; Frego, Mauro

    2014-01-01

    Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries, the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20% of all cases. Five years cumulative survival is less than 5% and rises to 25% for radically resected patients. About 40% has locally advanced in PC either borderline resectable (BRPC) or unresectable locally advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy (NT) has increasingly became a valid treatment option. The aim of NT is to reach local control of disease but, also, it is recognized to convert about 40% of LAPC patients to R0 resectability, thus providing a significant improvement of prognosis for responding patients. Once R0 resection is achieved, survival is comparable to that of early stage PCs treated by upfront surgery. Thus it is crucial to look for a proper patient selection. Neoadjuvant strategies are multiples and include neoadjuvant chemotherapy (nCT), and the association of nCT with radiotherapy (nCRT) given as either a combination of a radio sensitizing drug as gemcitabine or capecitabine or and concomitant irradiation or as upfront nCT followed by nRT associated to a radio sensitizing drug. This latter seem to be most promising as it may select patients who do not go on disease progression during initial treatment and seem to have a better prognosis. The clinical relevance of nCRT may be enhanced by the application of higher active protocols as FOLFIRINOX. PMID:25071332

  8. A Cell-Based Approach to Early Pancreatic Cancer Detection

    Science.gov (United States)

    2016-10-01

    Award Number: W81XWH-15-1-0457 TITLE: A Cell-Based Approach to Early Pancreatic Cancer Detection PRINCIPAL INVESTIGATOR: Dr. Ben Stanger...SUBTITLE 5a. CONTRACT NUMBER A Cell-Based Approach to Early Pancreatic Cancer Detection 5b. GRANT NUMBER W81XWH-15-1-0457 5c. PROGRAM ELEMENT NUMBER 6...pancreatic cancer patients. 15. SUBJECT TERMS Pancreatic cancer , metastasis, circulating tumor cells 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION

  9. Preclinical fluorescent mouse models of pancreatic cancer

    Science.gov (United States)

    Bouvet, Michael; Hoffman, Robert M.

    2007-02-01

    Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent protein (RFP). Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. We have shown a high correlation between florescent optical imaging and magnetic resonance imaging in these models. Alternatively, transplantation of RFP-expressing tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.

  10. Pancreatic cancer-Pathology%胰腺癌:病理学

    Institute of Scientific and Technical Information of China (English)

    Frank Bergmann; Irene Esposito; Esther Herpel; Peter Schirmacher

    2007-01-01

    @@ Introductions Pancreatic ductal adenocarcinoma (frequently simply being referred to as "pancreatic cancer") represents the most frequent neoplasm of the pancreas, accounting for 85% to 90% of all pancreatic tumors [1, 2].

  11. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  12. Pancreatic cancer, treatment options, and GI-4000

    Science.gov (United States)

    Hartley, Marion L; Bade, Najeebah A; Prins, Petra A; Ampie, Leonel; Marshall, John L

    2015-01-01

    Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year and only 6% will make it past 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors—RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials. PMID:25585100

  13. Pancreatic cancer and depression: myth and truth

    Directory of Open Access Journals (Sweden)

    Schmid Roland M

    2010-10-01

    Full Text Available Abstract Background Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression. However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se? Discussion Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy. Summary A review of the literature on this issue should reveal which are the facts and what is myth.

  14. Research advances in molecular targeted therapy for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    XU Ying

    2016-10-01

    Full Text Available Pancreatic cancer remains one of the malignant tumors with the worst prognosis, and its incidence is associated with Western diet, smoking, drinking, obesity, chronic pancreatitis, and a family history of pancreatic cancer. Currently, the treatment of pancreatic cancer focuses on surgery and chemotherapy, but no ideal therapeutic effect has been achieved. An understanding of the specific molecular mechanism of the development of pancreatic cancer helps to better prevent and treat pancreatic cancer. This article introduces the latest advances in the specific molecular mechanism of the development of pancreatic cancer and its targeted therapy and points out that molecular-targeted therapy in addition to traditional treatment helps to improve the prognosis of patients with pancreatic cancer.

  15. Embryonic stem cell factors and pancreatic cancer.

    Science.gov (United States)

    Herreros-Villanueva, Marta; Bujanda, Luis; Billadeau, Daniel D; Zhang, Jin-San

    2014-03-07

    Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy.

  16. Familial pancreatic cancer: Concept, management and issues

    Science.gov (United States)

    Matsubayashi, Hiroyuki; Takaori, Kyoichi; Morizane, Chigusa; Maguchi, Hiroyuki; Mizuma, Masamichi; Takahashi, Hideaki; Wada, Keita; Hosoi, Hiroko; Yachida, Shinichi; Suzuki, Masami; Usui, Risa; Furukawa, Toru; Furuse, Junji; Sato, Takamitsu; Ueno, Makoto; Kiyozumi, Yoshimi; Hijioka, Susumu; Mizuno, Nobumasa; Terashima, Takeshi; Mizumoto, Masaki; Kodama, Yuzo; Torishima, Masako; Kawaguchi, Takahisa; Ashida, Reiko; Kitano, Masayuki; Hanada, Keiji; Furukawa, Masayuki; Kawabe, Ken; Majima, Yoshiyuki; Shimosegawa, Toru

    2017-01-01

    Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion ( Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society. PMID:28246467

  17. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  18. Imaging and Endoscopic Approaches to Pancreatic Cancer.

    Science.gov (United States)

    Rosenthal, Michael H; Lee, Alexander; Jajoo, Kunal

    2015-08-01

    Imaging and endoscopy both play important and complementary roles in the initial diagnosis, staging, monitoring, and symptomatic management of pancreatic cancer. This article provides an overview of the uses of each of the diagnostic modalities, common imaging findings, alternative considerations, and areas of ongoing work in diagnostic imaging. This article also provides details of the uses of endoscopy for diagnosis, staging, and intervention throughout the course of a patient's care. These modalities each play important roles in the complex multidisciplinary care of patients with pancreatic cancer.

  19. [Persistence of chronic inflammatory responses, role in the development of chronic pancreatitis, obesity and pancreatic cancer].

    Science.gov (United States)

    Khristich, T N

    2014-11-01

    The purpose of the review--to analyze the basic data of the role of chronic low-intensity inflammatory response as general biological process in the development and progression of chronic pancreatitis, obesity, and pancreatic cancer. Highlighted evidence from epidemiological studies showing that chronic pancreatitis and obesity are independent risk factors for pancreatic cancer, regardless of diabetes. Studied role of adipokines as Cytokines regulating of immune inflammatory response. Draws attention to the staging of pancreatic cancer in obesity.

  20. Proteome-based biomarkers in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sun; Ann H Rosendahl; Daniel Ansari; Roland Andersson

    2011-01-01

    Pancreatic cancer, as a highly malignant cancer and the fourth cause of cancer-related death in world, is characterized by dismal prognosis, due to rapid disease progression, highly invasive tumour phenotype, and resistance to chemotherapy. Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved. A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis. Furthermore, biomarkers for targeting, directing and assessing therapeutic intervention, as well as for detection of residual or recurrent cancer are also needed. Thus, the identification of adequate biomarkers in pancreatic cancer is of extreme importance. Recently, accompanying the development of proteomic technology and devices, more and more potential biomarkers have appeared and are being reported. In this review, we provide an overview of the role of proteome-based biomarkers in pancreatic cancer, including tissue, serum, juice, urine and cell lines. We also discuss the possible mechanism and prospects in the future. That information hopefully might be helpful for further research in the field.

  1. Inflammation, Autophagy, and Obesity: Common Features in the Pathogenesis of Pancreatitis and Pancreatic Cancer

    OpenAIRE

    Gukovsky, Ilya; Li, Ning; Todoric, Jelena; Gukovskaya, Anna; Karin, Michael

    2013-01-01

    Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an env...

  2. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    OpenAIRE

    Lun Zhang; Jiahui Li; Liang Zong; Xin Chen; Ke Chen; Zhengdong Jiang; Ligang Nan; Xuqi Li; Wei Li; Tao Shan; Qingyong Ma; Zhenhua Ma

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concent...

  3. Review of screening for pancreatic cancer in high risk individuals

    OpenAIRE

    Stoita, Alina; Penman, Ian D; Williams, David B.

    2011-01-01

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in...

  4. Pancreatic Cancer Epidemiology, Detection, and Management

    Directory of Open Access Journals (Sweden)

    Qiubo Zhang

    2016-01-01

    Full Text Available PC (pancreatic cancer is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies.

  5. Pancreatic Cancer Epidemiology, Detection, and Management.

    Science.gov (United States)

    Zhang, Qiubo; Zeng, Linjuan; Chen, Yinting; Lian, Guoda; Qian, Chenchen; Chen, Shaojie; Li, Jiajia; Huang, Kaihong

    2016-01-01

    PC (pancreatic cancer) is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies.

  6. Controlled clinical study on pancreatic stenting in the relief of pain of advanced pancreatic cancer with dilated pancreatic duct

    Institute of Scientific and Technical Information of China (English)

    高飞

    2014-01-01

    Objective To explore the efficacy of pancreatic stenting in the relief of abdominal pain of advanced pancreatic cancer with dilated pancreatic duct.Methods A tolal of 61 patients with advanced pancreatic carcinoma companied with dilated pancreatic duct were divided into two groups.Twenty-eight cases(two cases were excluded because of stent loss)in stent group treated with

  7. Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Chao Ma; Zhuan Liao; Bing Tian; Jian-Ping Lu

    2011-01-01

    AIM: To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases. METHODS: There were 15 patients in the present study, among whom 10 had pancreatic cancer and 5, chronic pancreatitis. In all patients, pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncreas. Pathology data of all pa tients was confirmed by biopsy and surgery. Among the 10 patients with pancreatic cancer, 3 people had a medical history of longterm alcohol consumption. Of 5 patients with chronic pancreatitis, 4 men suffered from alcoholic chronic pancreatitis. Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography. Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences. The parameters were as follows: spectral width, 15 KHz; time domain, 64 K; number of scans, 512; and acquisition time, 2.128 s. RESULTS: The main component of pancreatic juice included leucine, iso-leucine, valine, lactate, alanine, acetate, aspartate, lysine, glycine, threonine, tyrosine, histidine, tryptophan, and phenylalanine. On performing 1D 1H and 2D total correlation spectroscopy, we found a triplet peak at the chemical shift of 1.19 ppm, which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis. This triplet peak was considered the resonance of the methyl of ethoxy group, which may be associated with the metabolism of alcohol in the pancreas. CONCLUSION: The triplet peak, at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

  8. Molecular Targeted Intervention for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2015-08-01

    Full Text Available Pancreatic cancer (PC remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies.

  9. Molecular Targeted Intervention for Pancreatic Cancer

    Science.gov (United States)

    Mohammed, Altaf; Janakiram, Naveena B.; Pant, Shubham; Rao, Chinthalapally V.

    2015-01-01

    Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID:26266422

  10. Ultrasound-enhanced nanotherapy of pancreatic cancer

    Science.gov (United States)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

    2010-03-01

    The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

  11. Medical history, diet and pancreatic cancer.

    Science.gov (United States)

    La Vecchia, C; Negri, E; D'Avanzo, B; Ferraroni, M; Gramenzi, A; Savoldelli, R; Boyle, P; Franceschi, S

    1990-01-01

    The relation between various aspects of medical history, selected indicator foods and the risk of pancreatic cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 247 patients with cancer of the pancreas, and 1,089 controls in hospitals for acute, nonneoplastic or digestive conditions. There was a significant association with history of pancreatitis (relative risk, RR 3.2, 95% confidence interval = 1.3-7.9), which was however reduced when the condition was first diagnosed at least 5 years previously. The point estimates were slightly, but not significantly, above unity for diabetes (RR = 1.5), gastrectomy (RR = 1.1) and cholelithiasis (RR = 1.3), and no association was found with liver disease or drug allergy. In relation to diet, there was some tendency for the risk to decrease with more frequent fruit consumption, but the results were largely inconsistent in relation to various indicators of meat, animal protein or fat intake. Although no important associations were found in this study with various aspects of medical history or diet indicators and pancreatic cancer risk, on account of the size of the dataset and the statistical power, this study contributes usefully to the debate on a common cancer whose causes are still largely undefined.

  12. Evaluation of Trace Elements in Pancreatic Cancer Patients in Iran

    Directory of Open Access Journals (Sweden)

    Leila Farzin

    2013-04-01

    Full Text Available Background: Pancreatic cancer is a major worldwide health problem. Little is known about the etiology of pancreatic cancer, which is an important cause of cancer mortality in developed countries. This study evaluates the importance of amounts of trace elements in pancreatic cancer etiology and diagnostics.Methods: Atomic absorption spectrometry was used to estimate zinc, selenium, copper, cadmium and lead concentrations in 80 patients with pancreatic cancer admitted to various hospitals in Tehran Province over an 18-month period and in 100 control subjects.Results: There were significantly lower levels (P0.05.Conclusion: In this study and by analyzing data from recent major reported series, we have found that cadmium is a plausible pancreatic carcinogen. This study also suggests a significant relationship between zinc metabolism and pancreatic cancer.

  13. Aberrant expression of Wnt antagonist SFRP1 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    BU Xian-min; ZHAO Cheng-hai; DAI Xian-wei

    2008-01-01

    @@ Pancreatic cancer is one of the malignant tumor with a very poor prognosis. Both genetic and epigenetic alterations are involved in the pathogenetic mechanisms of pancreatic cancer. Hypermethylation and subsequent loss of expression of some tumor suppressor genes and tumor-related genes occur frequently in pancreatic cancer, such as loss of expression of pl6,1 RASSF1A,2 SOCS-1,3 and hMLH14 genes were repoted.

  14. Pancreatic Cancer: Are We Moving Forward Yet?

    OpenAIRE

    Muhammad Wasif Saif

    2007-01-01

    Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5-FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva®) are currently the only standard chemotherapeutic agents approved by FDA for the t...

  15. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  16. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    Science.gov (United States)

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  17. Tumor antigens as related to pancreatic cancer.

    Science.gov (United States)

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  18. Pancreatic cancer cachexia: A review of mechanisms and therapeutics

    Directory of Open Access Journals (Sweden)

    Carlyn Rose Tan

    2014-03-01

    Full Text Available Over the last decade, we have gained new insight into the pathophysiology of pancreatic cancer cachexia. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.

  19. [Pancreatitis, pancreatic cancer and obesity: hypothesis and facts].

    Science.gov (United States)

    Grigor'eva, I N; Efimova, O V; Suvorova, T S; Tov, N L

    2014-01-01

    THE PURPOSE OF THE REVIEW: Analyze the basic data on the role of obesity in the pathogenesis of pancreatic cancer (PC) and the modern mechanisms of this association. In the European Union and in Russia incidence of pancreatic diseases increases, such pancreatic cancer (PC) ranks 10th among cancer diseases. Obesity is a risk factor for not only of severe acute pancreatitis, but also PC at that independently of diabetes. In a meta-analysis the PC risk in obese increased by 47%, while the person with a central obesity have a higher PC risk compared to those with a peripheral type of obesity (odds ratio = 1,45, 95% CI: 1,02-2,07), but association between BMI and PC risk in this Japanese population may be different from that in Western populations, sometimes inversely. The link between obesity and PC is explained by insulin resistance and hyperinsulinemia: was proved a direct correlation between the level of circulating C-peptide and PC, low levels of serum adiponektin and leptin increase the PC risk. There are also genetic risk factors for PC: a statistically significant interaction between IVS1-27777C> and IVS1-23525A>T genotypes of the FTO gene with obesity and the PC risk: AA genotype in patients with BMI < 25 kg/m2 reduced PC risk by 22%-28% (p < 0,0001), and with BMI ≥ 25 kg/m2 was associated with 54%-60% increased PC risk (p < 0,0015). Lifestyle factors (smoking, consumption of saturated fats, etc.) increase the PC risk.

  20. A Proteomic Comparison of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue from Autoimmune Pancreatitis, Chronic Pancreatitis, and Pancreatic Cancer

    Science.gov (United States)

    Paulo, Joao A; Kadiyala, Vivek; Brizard, Scott; Banks, Peter A; Steen, Hanno; Conwell, Darwin L

    2015-01-01

    Context Formalin-fixed paraffin-embedded (FFPE) tissue is a standard for specimen preservation, and as such FFPE tissue banks are an untapped resource of histologically-characterized specimens for retrospective biomarker investigation for pancreatic disease. Objectives We use liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to compare FFPE specimens from three different diseases of the exocrine pancreas. Design We investigated the proteomic profile of FFPE pancreatic tissue from 9 archived specimens that were histologically classified as: autoimmune pancreatitis (n=3), chronic pancreatitis (n=3), and pancreatic cancer (n=3), using LC-MS/MS. Setting This is a proteomic analysis experiment of FFPE pancreatic tissue in an academic center. Patients FFPE tissue specimens were provided by Dana-Farber/Harvard Cancer Center (Boston, MA, USA). Interventions FFPE tissue specimens were collected via routine surgical resection procedures. Main outcome measures We compared proteins identified from chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer FFPE pancreatic tissue. Results We identified 386 non-redundant proteins from 9 specimens. Following our filtering criteria, 73, 29, and 53 proteins were identified exclusively in autoimmune pancreatitis, chronic pancreatitis, and pancreatic cancer specimens, respectively. Conclusions We report that differentially-expressed proteins can be identified among FFPE tissues specimens originating from individuals with different histological diagnoses. These proteins merit further confirmation with a greater number of specimens and orthogonal validation, such as immunohistochemistry. The mass spectrometry-based methodology used herein has the potential to enhance diagnostic biomarker and therapeutic target discovery, further advancing pancreatic research. PMID:23846938

  1. Blood Type Influences Pancreatic Cancer Risk | Division of Cancer Prevention

    Science.gov (United States)

    A variation in the gene that determines ABO blood type influences the risk of pancreatic cancer, according to the results of the first genome-wide association study (GWAS) for this highly lethal disease. The genetic variation, a single nucleotide polymorphism (SNP), was discovered in a region of chromosome 9 that harbors the gene that determines blood type, the researchers reported August 2 online in Nature Genetics. |

  2. Biomarkers and Pharmacogenetics in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Xunhai Xu

    2011-07-01

    Full Text Available Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs that is associated with positive efficacy of gemcitabine (Abstract #4022; the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657; the re-affirmation of plasma cytidine deaminase (CDA as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645; and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO trial in an attempt for epidermal growth factor receptor (EGFR pathway biomarker identifications (Abstract #4047

  3. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Shin [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Hamada, Hirofumi [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan); Kobune, Masayoshi [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan); Satoh, Kennichi [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  4. Assessment value of quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jiang-Xia Lei

    2016-01-01

    Objective:To analyze the assessment value of the quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer.Methods:A total of 58 patients with space-occupying pancreatic lesions were divided into 20 patients with pancreatic cancer and 38 patients with benign pancreatic lesions after pancreatic CT perfusion. Patients with pancreatic cancer received palliative surgery, and the cancer tissue and para-carcinoma tissue specimens were collected during operation. The differences in pancreatic CT perfusion scanning parameter values and serum tumor marker levels were compared between patients with pancreatic cancer and patients with benign pancreatic lesions, mRNA expression levels of malignant molecules in pancreatic cancer tissue and para-carcinoma tissue were further determined, and the correlation between pancreatic CT perfusion scanning parameter values and malignant degree of pancreatic cancer was analyzed.Results:CT perfusion scanning BF, BV and Per values of patients with pancreatic cancer were lower than those of patients with benign pancreatic lesions; serum CA19-9, CEA, CA125 and CA242 levels were higher than those of patients with benign pancreatic lesions (P<0.05); mRNA expression levels of Bcl-2, Bcl-xL andsurvivin in pancreatic cancer tissue samples were higher than those in para-carcinoma tissue samples, and mRNA expression levels ofP53 andBax were lower than those in para-carcinoma tissue samples (P<0.05); CT perfusion scanning parameters BF, BV and Per values of patients with pancreatic cancer were negatively correlated with CA19-9, CEA, CA125 and CA242 levels in serum as well as mRNA expression levels ofBcl-2, Bcl-xL and survivinin pancreatic cancer tissue, and positively correlated with mRNA expression levels ofP53andBaxin pancreatic cancer tissue (P<0.05).Conclusions:Pancreatic CT perfusion scanning is a reliable way to judge the malignant degree of pancreatic cancer and plays a positive role in guiding clinical

  5. What's New in Pancreatic Cancer Research and Treatment?

    Science.gov (United States)

    ... trials. Drugs that target cancer stem cells: One theory as to why pancreatic cancer is difficult to ... Us Local Offices Employment Become a Supplier Report Fraud or Abuse Global Health ACS CAN Sign Up ...

  6. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  7. Desmoplasia and Chemoresistance in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Marvin Schober

    2014-10-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC occurs mainly in people older than 50 years of age. Although great strides have been taken in treating PDAC over the past decades its incidence nearly equals its mortality rate and it was quoted as the 4th leading cause of cancer deaths in the U.S. in 2012. This review aims to focus on research models and scientific developments that help to explain the extraordinary resistance of PDAC towards current therapeutic regimens. Furthermore, it highlights the main features of drug resistance including mechanisms promoted by cancer cells or cancer stem cells (CSCs, as well as stromal cells, and the acellular components surrounding the tumor cells—known as peritumoral desmoplasia—that affects intra-tumoral drug delivery. Finally, therapeutic concepts and avenues for future research are suggested, based on the topics discussed.

  8. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Akimasa [Department of Surgery II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2010-11-24

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated.

  9. Marantic Endocarditis Associated with Pancreatic Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Gayle S. Jameson

    2009-04-01

    Full Text Available Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis (NBTE, is a well-documented phenomenon due to hypercoagulability from an underlying cause. It has been associated with a variety of inflammatory states including malignancy. Surprisingly, although hypercoagulability is often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population. We report three cases of marantic endocarditis in patients with advanced pancreatic cancer. In two instances, the patients’ neurological symptoms preceded the diagnosis of advanced pancreatic cancer. Health care professionals should be alert to the possibility of marantic endocarditis in any patient with cancer, especially pancreatic cancer, who presents with symptoms of neurological dysfunction or an arterial thrombotic event. Prompt diagnosis and treatment with heparin, unfractionated or low molecular weight, may prevent catastrophic CNS events and decrease morbidity in patients with pancreatic cancer and other malignancies.

  10. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Lun Zhang

    2016-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy.

  11. Indicative findings of pancreatic cancer in prediagnostic CT

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea); Kim, Myeong-Jin [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea); Yonsei University College of Medicine, Institute of Gastroenterology and Brain Korea 21 project, Seoul (Korea); Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea)

    2009-10-15

    We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

  12. How fibrosis influences imaging and surgical decisions in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Mert eErkan

    2012-10-01

    Full Text Available Our understanding of pancreatic ductal adenocarcinoma is shifting away from a disease of malignant ductal cells-only, towards a complex system where tumor evolution is a result of interaction of cancer cells with their microenvironment. This change has led to intensification of research focusing on the fibrotic stroma of pancreatic ductal adenocarcinoma. Pancreatic stellate cells are the main fibroblastic cells of the pancreas which are responsible for producing the desmoplasia in chronic pancreatitis and pancreatic ductal adenocarcinoma. Clinically, the effect of desmoplasia is two-sided; on the negative side it is a hurdle in the diagnosis of pancreatic ductal adenocarcinoma because the fibrosis in cancer resembles that of chronic pancreatitis. It is also believed that pancreatic stellate cells and pancreatic fibrosis are partially responsible for the therapy resistance in pancreatic cancer. On the positive side, a fibrotic pancreas is safer to operate on compared to a fatty and soft pancreas which is prone for postoperative pancreatic fistula. In this review the impact of pancreatic fibrosis on diagnosis of pancreatic cancer and surgical decisions are discussed from a clinical point of view.

  13. Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer

    Science.gov (United States)

    Liu, Tao; Gou, Shan-Miao; Wang, Chun-You; Wu, He-Shui; Xiong, Jiong-Xin; Zhou, Feng

    2007-01-01

    AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1 protein was measured by Western blot and immunohistochemistry. Immunohistochemistry was also used to detect proliferative cell nuclear antigen (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation, were analyzed by using χ2 test. RESULTS: Immunohistochemistry showed that 41.1% of pancreatic cancers were positive for PDX-1 expression, but normal pancreatic tissue except islets showed no staining for PDX-1. In consistent with the result of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher in pancreatic cancer tissues than normal pancreatic tissues (2-3.56 ± 0.35 vs 2-8.76 ± 0.14, P < 0.01). Lymph node metastasis (P < 0.01), TNM grading (P < 0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01) were significantly correlated with PDX-1 expression levels. CONCLUSION: PDX-1 is re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1-positive cells may be tumor stem cells and PDX-1 may act as alternate surface marker of pancreatic cancer stem cells. PMID:17552012

  14. Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Tao Liu; Shan-Miao Gou; Chun-You Wang; He-Shui Wu; Jiong-Xin Xiong; Feng Zhou

    2007-01-01

    AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic cancer characteristics,incluling pathological grading, TNM grading, tumor metastasis and tumor cell proliferation.METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1 protein was measured by Western blot and immunohistochemistry.Immunohistochemistry was also used to detect proliferative cell nuclear antigen (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation, were analyzed by using χ2 test.RESULTS: Immunohistochemistry showed that 41.1% of pancreatic cancers were positive for PDX-1 expression,but normal pancreatic tissue except islets showed no staining for PDX-1. In consistent with the result of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher in pancreatic cancer tissues than normal pancreatic tissues (2-3.56 ± 0.35 vs 2-8.76 ± 0.14, P< 0.01). Lymph node metastasis (P < 0.01), TNM grading (P < 0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01) were significantly correlated with PDX-1 expression levels.CONCLUSION: PDX-1 is re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1-positive cells may be tumor stem cells and PDX-1 may act as alternate surface marker of pancreatic cancer stem cells.

  15. Management of pancreatic cancer in the elderly.

    Science.gov (United States)

    Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

    2016-01-14

    Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

  16. New targeted therapies in pancreatic cancer.

    Science.gov (United States)

    Seicean, Andrada; Petrusel, Livia; Seicean, Radu

    2015-05-28

    Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

  17. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kikuta, Kazuhiro [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Egawa, Shinichi; Unno, Michiaki [Department of Hepatobiliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2010-12-17

    Research highlights: {yields} Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. {yields} Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. {yields} PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. {yields} This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated {beta}-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered

  18. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xiao-Ling Ding; Jie-Fei Huang; Hong Zhang; Sheng-Bao Wu; Jian-Ping Cheng; Qun Wei

    2008-01-01

    AIM:To investigate apoptosis in human pancreatic cancer ceils induced by Triptolide (TL),and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax.METHODS:Human pancreatic cancer cell line SW1990 was cultured in DIEM media for this study.MTT assay was used to determine the cell growth inhibitory rate in vitro.Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment.RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax.RESULTS:TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner.TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics.TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h,the apoptotic rates of human pancreatic cancer cells increased significantly.RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not.CONCLUSION:TL is able to induce the apoptosis in human pancreatic cancer cells.This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.

  19. Cholecystokinin and pancreatic cancer: the chicken or the egg?

    Science.gov (United States)

    Smith, Jill P; Solomon, Travis E

    2014-01-01

    The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."

  20. Salivary MicroRNA in Pancreatic Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Marine Humeau

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in Western countries, with the lowest 1-year survival rate among commonly diagnosed cancers. Reliable biomarkers for pancreatic cancer diagnosis are lacking and are urgently needed to allow for curative surgery. As microRNA (miRNA recently emerged as candidate biomarkers for this disease, we explored in the present pilot study the differences in salivary microRNA profiles between patients with pancreatic tumors that are not eligible for surgery, precancerous lesions, inflammatory disease or cancer-free patients as a potential early diagnostic tool.Whole saliva samples from patients with pancreatic cancer (n = 7, pancreatitis (n = 4, IPMN (n = 2, or healthy controls (n = 4 were obtained during endoscopic examination. After total RNA isolation, expression of 94 candidate miRNAs was screened by q(RTPCR using Biomark Fluidgm. Human-derived pancreatic cancer cells were xenografted in athymic mice as an experimental model of pancreatic cancer.We identified hsa-miR-21, hsa-miR-23a, hsa-miR-23b and miR-29c as being significantly upregulated in saliva of pancreatic cancer patients compared to control, showing sensitivities of 71.4%, 85.7%, 85,7% and 57%, respectively and excellent specificity (100%. Interestingly, hsa-miR-23a and hsa-miR23b are overexpressed in the saliva of patients with pancreatic cancer precursor lesions. We found that hsa-miR-210 and let-7c are overexpressed in the saliva of patients with pancreatitis as compared to the control group, with sensitivity of 100% and 75%, and specificity of 100% and 80%, respectively. Last hsa-miR-216 was upregulated in cancer patients as compared to patients diagnosed with pancreatitis, with sensitivity of 50% and specificity of 100%. In experimental models of PDAC, salivary microRNA detection precedes systemic detection of cancer cells markers.Our novel findings indicate that salivary miRNA are discriminatory in pancreatic cancer patients

  1. c-Met in pancreatic cancer stem cells: Therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Aizpea Zubia-Olascoaga; Luis Bujanda

    2012-01-01

    Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths.Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease.The identification of CSC markers could lead to the development of new therapeutic targets.In this study,the authors explore the functional role of c-Met in pancreatic CSCs,by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice.They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Methigh in a higher tumorigenic cancer cell population.Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs.In pancreatic tumors established in NOD SCID mice,c-Met inhibition slowed tumor growth and reduced the population of CSCs,along with preventing the development of metastases.

  2. Genetic factors affecting patient responses to pancreatic cancer treatment

    Science.gov (United States)

    Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

    2016-01-01

    Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. PMID:27708512

  3. Metformin suppresses sonic hedgehog expression in pancreatic cancer cells.

    Science.gov (United States)

    Nakamura, Masafumi; Ogo, Ayako; Yamura, Masahiro; Yamaguchi, Yoshiyuki; Nakashima, Hiroshi

    2014-04-01

    Metformin use has previously been associated with decreased cancer risk. The Hedgehog signaling pathway is a well-characterized early and late mediator of pancreatic cancer oncogenesis. The aim of the present study was to clarify the effect of metformin on factors involved in Hedgehog signaling. BxPC3 human pancreatic cancer cells were treated with metformin, and Sonic hedgehog (Shh) mRNA and protein levels were examined by real time reverse transcription-polymerase chain reaction, immunohistochemistry and immunoblotting, respectively. The effect of metformin on Shh levels was also examined in three other cancer cell lines. Shh protein and mRNA expression was suppressed by metformin in BxPC3 cells. This phenomenon was further confirmed in three other cancer cell lines. Shh mRNA expression was inhibited by metformin in a concentration-dependent manner in two cancer cell lines. Metformin reduces the expression of Shh in several cancer cell lines including pancreatic cancer cell.

  4. Review of screening for pancreatic cancer in high risk individuals

    Institute of Scientific and Technical Information of China (English)

    Alina Stoita; Ian D Penman; David B Williams

    2011-01-01

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results.

  5. Review of screening for pancreatic cancer in high risk individuals.

    Science.gov (United States)

    Stoita, Alina; Penman, Ian D; Williams, David B

    2011-05-21

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results.

  6. Selected cytokines in patients with pancreatic cancer: a preliminary report.

    Directory of Open Access Journals (Sweden)

    Wojciech Błogowski

    Full Text Available BACKGROUND/AIMS: Recent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting. METHODS: In this study, we examined the levels of a broad panel of cytokines, including interleukin (IL-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα and granulocyte-colony stimulating factor (G-CSF in patients with pancreatic adenocarcinoma (n=43, other pancreatic malignancies (neuroendocrine [n=10] and solid pseudopapillary tumors [n=3], and healthy individuals (n=41. RESULTS: We found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03. Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p=0.002. Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%-82%. CONCLUSIONS: Our study i supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.

  7. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  8. The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer

    OpenAIRE

    Abel, Ethan V.; Kim, Edward J.; Jingjiang Wu; Mark Hynes; Filip Bednar; Erica Proctor; Lidong Wang; Dziubinski, Michele L; Simeone, Diane M.

    2014-01-01

    Background Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. Methods Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhi...

  9. ANTI CANCER ACTIVITY OF PHYLLANTHUS AMARUS IN AZASERINE INDUCED PANCREATIC CANCER OF WISTAR RATS

    OpenAIRE

    Ankit Prajapati; Sunant Raval; TapanVaria

    2015-01-01

    Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer is adeno-carcinoma. The present experiment was carried out to study histopathological changes occur in pancreas in different groups of azaserine induced pancreatic cancer in Wistar rats with and without the treatment of aqueous and alcoholic extract of Phyllanthus amarus at different doses. Histopathological examination of ...

  10. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  11. Transversal Descriptive Study of Xenobiotic Exposures in Patients with Chronic Pancreatitis and Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Cara Yvonne Jeppe

    2008-03-01

    Full Text Available There have been a substantial number of reports in the literature linking pancreatitis and pancreatic cancer to certain xenobiotics and occupations. It has been hypothesized that exposure to volatile hydrocarbons and particularly petrochemicals increases susceptibility to pancreatitis. We performed a study aimed to enumerate occupational and environmental xenobiotics described in the literature as potential risk factors for pancreatitis and to document exposures to these in chronic pancreatitis patients presenting with chronic pain for surgery.

  12. Is metastatic pancreatic cancer an untargetable malignancy?

    Institute of Scientific and Technical Information of China (English)

    Hampig Raphael Kourie; Joseph Gharios; Fadi Elkarak; Joelle Antoun; Marwan Ghosn

    2016-01-01

    Metastatic pancreatic cancer(MPC) is one of the most aggressive malignancies, known to be chemo-resistant and have been recently considered resistant to some targeted therapies(TT). Erlotinib combined to gemcitabine is the only targeted therapy that showed an overall survival benefit in MPC. New targets and therapeutic approaches, based on new-TT, are actually being evaluated in MPC going from immunotherapy, epigenetics, tumor suppressor gene and oncogenes to stromal matrix regulators. We aim in this paper to present the major causes rendering MPC an untargetable malignancy and to focus on the new therapeutic modalities based on TT in MPC.

  13. Screening and Detection of Pancreatic Cancer

    Science.gov (United States)

    Gonda, Tamas A; Lucas, Aimee; Saif, Muhammad Wasif

    2014-01-01

    Summary Screening and early detection of pancreatic cancer has the potential to substantially impact outcomes in this deadly disease. Over the last ten years several cohort studies have been conducted and report on the yield of screening in high risk populations. With better understanding of the cellular compartments and the genetic and epigenetic changes that occur, biomarkers have also emerged as promising means of early detection. In this paper we summarize the results of the latest screening cohort and highlight a novel proteomic approach that may be used in future biomarker studies. PMID:21737887

  14. ANTI CANCER ACTIVITY OF PHYLLANTHUS AMARUS IN AZASERINE INDUCED PANCREATIC CANCER OF WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Ankit Prajapati

    2015-06-01

    Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer is adeno-carcinoma. The present experiment was carried out to study histopathological changes occur in pancreas in different groups of azaserine induced pancreatic cancer in Wistar rats with and without the treatment of aqueous and alcoholic extract of Phyllanthus amarus at different doses. Histopathological examination of pancreas of untreated group of rats showed hyperplasia of pancreatic duct, necrosis, fatty changes, haemorrhages between pancreatic cells. The rats treated with Phyllanthus amarus extracts showed no pathological lesions.

  15. Spontaneous regression of pancreatic cancer: Real or a misdiagnosis?

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Spontaneous tumor regression has been subject of numerous studies and speculations for many years.This phenomenon is exceptional,but well reported,in some types of tumors,but not in pancreatic cancer.Pancreatic cancer has the worst five-year survival rate of any cancer.Despite numerous molecular studies and clinical approaches,using several mouse models,this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive.Although pancreatic cancer tumors seldom undergo spontaneous regression,and some authors take that with skepticism,there are some cases reported in the literature.However,the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis.Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential.Diseases such as pancreatic benign tumors,insulinomas,or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer.Here we review different cases reported,their clinical characteristics,and possible mechanisms leading to spontaneous regression of pancreatic cancer.We also discuss the possibilities of misdiagnosis.

  16. Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery

    Science.gov (United States)

    2016-10-19

    Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

  17. Family history of cancer and risk of pancreatic cancer : a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    NARCIS (Netherlands)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H. M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could

  18. Invasion and metastasis in pancreatic cancer.

    Science.gov (United States)

    Keleg, Shereen; Büchler, Peter; Ludwig, Roman; Büchler, Markus W; Friess, Helmut

    2003-01-22

    Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well. Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival. During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth. The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis. In this review we highlight the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.

  19. Clinical significance of plasma metastin level in pancreatic cancer patients.

    Science.gov (United States)

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  20. Small molecule tyrosine kinase inhibitors in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    2008-10-01

    Full Text Available Sachin Gupta, Bassel F El-RayesDepartment of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, MI, USAAbstract: Pancreatic cancer has proven to be chemo-resistant, with gemcitabine being the only cytotoxic agent approved for advanced pancreatic cancer since 1996. Tyrosine kinase inhibitors represent a newer generation of chemotherapeutic agents targeting specific tumor pathways associated with carcinogenesis including cell cycle control, signal transduction, apoptosis and angiogenesis. These agents present a more selective way of treating pancreatic cancer. Erlotinib is the prototype of the tyrosine kinase inhibitors with proven efficacy in advanced pancreatic cancer and has been recently approved in that setting. Multiple other tyrosine kinase inhibitors targeting the VEGFR, PDGFR, and Src kinases are in various phases of clinical trials testing. The preliminary results of these trials have been disappointing. Current challenges in pancreatic cancer clinical trials testing include improving patient selection, identifying effective combinations, improving the predictive value of current preclinical models and better study designs. This review summarizes the present clinical development of tyrosine kinase inhibitors in pancreatic cancer and strategies for future drug development.Keywords: pancreatic cancer, erlotinib, tyrosine kinase inhibitors

  1. Epigenetics and pancreatic cancer: pathophysiology and novel treatment aspects.

    Science.gov (United States)

    Neureiter, Daniel; Jäger, Tarkan; Ocker, Matthias; Kiesslich, Tobias

    2014-06-28

    An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16(ink4a), are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

  2. Significant association between ABO blood group and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Julia; B; Greer; Mark; H; Yazer; Jay; S; Raval; M; Michael; Barmada; Randall; E; Brand; David; C; Whitcomb

    2010-01-01

    AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO bloo...

  3. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Directory of Open Access Journals (Sweden)

    Hannah Arem

    Full Text Available Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN totaling 213 single nucleotide polymorphisms (SNPs, and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L for the most significant SNPs using a subset of cohort cases (n = 713 and controls (n = 878. The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830. Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186, LRP2 (rs4668123, CYP24A1 (rs2762932, GC (rs2282679, and CUBN (rs1810205 genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037, but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  4. Pancreatic Cancer: Updates on Translational Research and Future Applications

    Directory of Open Access Journals (Sweden)

    Evangelos G Sarris

    2013-03-01

    Full Text Available Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3 gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.

  5. Radical resection of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexander Koliopanos; C Avgerinos; Athanasios Farfaras; C Manes; Christos Dervenis

    2008-01-01

    BACKGROUND:Pancreatic adenocarcinoma (PCa) is a disease with dismal prognosis, and the only possibility of cure, albeit small, is based on the combination of complete resection with negative histopathological margins (R0 resection) with adjuvant treatment. Therefore, a lot of effort has been made during the last decade to assess the role of extensive surgery in both local recurrence and survival of patients with PCa. DATA SOURCES:Medline search and manual cross-referencing were utilized to identify published evidence-based data for PCa surgery between 1973 and 2006, with emphasis to feasibility, efifcacy, long-term survival, disease free survival, recurrence rates, pain relief and quality of life. RESULTS: Extended surgery is safe and feasible in high volume surgical centers with comparable short-term results. Organ preserving surgery is a main goal because of quality of life reasons and is performed whenever possible from the tumor extent. Concerning long-term survival major vein resection does not adversely affect outcome. To date, there are no changes in long-term survival attributed to the extended lymph node dissection. However, there is a beneift in locoregional control with fewer local recurrences and extended lymphadenectomy allows better staging for the disease. CONCLUSIONS:Extended PCa surgery is safe and feasible despite the inconclusive results in patient's survival beneift. In the future, appropriately powered randomized trials of standard vs. extended resections may show improved outcomes for PCa patients.

  6. Occupational exposures and risk of pancreatic cancer.

    Science.gov (United States)

    Santibañez, Miguel; Vioque, Jesús; Alguacil, Juan; de la Hera, Manuela García; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-10-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  7. Core signaling pathways and new therapeutic targets in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    YOU Lei; CHEN Ge; ZHAO Yu-pei

    2010-01-01

    Objective Pancreatic cancer is a highly aggressive malignancy that has been resistant to treatment. Advances in cancer genetics have improved our understanding of this disease, but the genetics of pancreatic cancer remain poorly understood. A better understanding of the pathogenic role of specific gene mutations and core signaling pathways would propel the development of more effective treatments. The objective in this review was to highlight recent research that shows promise for new treatments for pancreatic cancer. Data sources All articles cited in this review were mainly searched from PubMed, which were published in English from 1993 to 2009. Study selection Original articles and critical reviews selected were relevant to the molecular mechanisms of pancreatic cancer. Results Dysregulation of core signaling pathways and processes through frequently genetic alterations can explain the major features of pancreatic tumorigenesis. New therapeutic targets based on recent research are emerging that hold promise for the future management of pancreatic cancer. Conclusion New agents used in conjunction with standard radiotherapy and chemotherapy might help to overcome drug resistance by targeting multiple signaling pathways to induce responsiveness of pancreatic cancer cells to death signals.

  8. Precursor lesions in pancreatic cancer: morphological and molecular pathology.

    Science.gov (United States)

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James

    2011-04-01

    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

  9. Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility.

    Science.gov (United States)

    Yamazaki, Ken; Takamura, Masaaki; Masugi, Yohei; Mori, Taisuke; Du, Wenlin; Hibi, Taizo; Hiraoka, Nobuyoshi; Ohta, Tsutomu; Ohki, Misao; Hirohashi, Setsuo; Sakamoto, Michiie

    2009-04-01

    Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.

  10. Limitation of CT in diagnosis of pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Honda, Hiroshi (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine); Kusumoto, Shizuo; Nishikawa, Kiyoshi (and others)

    The differentiation of pancreatic abnormalities remains a problem. We analyzed the sensitivity and specificity of computed tomography (CT) in the diagnosis of pancreatic disease, using six radiologists who had less than six months' training in CT (resident level: inexperienced) and six who had more than 12 months' training (staff level: experienced) in order to clarify the difficulty with CT in the qualitative diagnosis of pancreatic cancer. We reviewed retrospectively 100 cases: 28 cases of pancreatic cancer, 15 of chronic pancreatitis, three of acute pancreatitis, 12 of neoplastic disease that involved the pancreas, and 42 normal subjects. The average sensitivity and specificity of CT in the diagnosis of pancreatic disease were 81.3% and 84.4%, respectively, for the experienced radiologists and 64.0% and 82.1%, respectively, for the inexperienced radiologists. The averages for pancreatic cancer were 65.3% and 87.8% for the experienced radiologists and 60.7% and 87.3% for the inexperienced radiologists. We conclude that the ability to detect pancreatic abnormalities improves with training and experience, but diagnosis of pancreatic cancer does not improve after a certain level of expertise. (author).

  11. [Surgery for pancreatic cancer: Evidence-based surgical strategies].

    Science.gov (United States)

    Sánchez Cabús, Santiago; Fernández-Cruz, Laureano

    2015-01-01

    Pancreatic cancer surgery represents a challenge for surgeons due to its technical complexity, the potential complications that may appear, and ultimately because of its poor survival. The aim of this article is to summarize the scientific evidence regarding the surgical treatment of pancreatic cancer in order to help surgeons in the decision making process in the management of these patients .Here we will review such fundamental issues as the need for a biopsy before surgery, the type of pancreatic anastomosis leading to better results, and the need for placement of drains after pancreatic surgery will be discussed.

  12. Comparison of Uncinate Process Cancer and Non-Uncinate Process Pancreatic Head Cancer.

    Science.gov (United States)

    Liu, Chang; Tian, Xiaodong; Xie, Xuehai; Gao, Hongqiao; Zhuang, Yan; Yang, Yinmo

    2016-01-01

    The special anatomical position accounts for unusual clinicopathological features of uncinate process cancer. This study aimed to compare clinicopathological features of patients with uncinate process cancer to patients with non-uncinate process pancreatic head cancer. Total 160 patients with pancreatic head cancer were enrolled and classified into two groups: uncinate process cancer and non-uncinate process pancreatic head cancer. We found that the ratio of vascular invasion was significantly higher in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In addition, the rate of R1 resection was significantly higher in patients with uncinate process cancer. Furthermore, the median disease-free survival (11 months vs. 15 months, p=0.043) and overall survival (15 months vs. 19 months, p=0.036) after R0 resection were lower for uncinate process cancer. Locoregional recurrence was more frequent (p=0.017) and earlier (12 months vs. 36 months; p=0.002) in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In conclusion, uncinate process cancer is more likely to invade blood vessel and has worse prognosis due to the earlier and more frequent locoregional recurrence.

  13. The Smad family and its role in pancreatic cancer.

    Science.gov (United States)

    Singh, P; Wig, J D; Srinivasan, R

    2011-01-01

    One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  14. Genomic alterations in pancreatic cancer and their relevance to therapy

    Institute of Scientific and Technical Information of China (English)

    Erina; Takai; Shinichi; Yachida

    2015-01-01

    Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.

  15. ABO blood group and the risk of pancreatic cancer.

    Science.gov (United States)

    Wolpin, Brian M; Chan, Andrew T; Hartge, Patricia; Chanock, Stephen J; Kraft, Peter; Hunter, David J; Giovannucci, Edward L; Fuchs, Charles S

    2009-03-18

    Other than several rare, highly penetrant familial syndromes, genetic risk factors for sporadic pancreatic cancer are largely unknown. ABO blood type is an inherited characteristic that in previous small studies has been associated with the risk of gastrointestinal malignancies. We separately examined the relationship between ABO blood type and the risk of incident pancreatic cancer in two large, independent, prospective cohort studies (the Nurses' Health Study and Health Professionals Follow-up Study) that collected blood group data on 107 503 US health professionals. Hazard ratios for pancreatic cancer by ABO blood type were calculated using Cox proportional hazards models with adjustment for other known risk factors, including age, tobacco use, body mass index, physical activity, and history of diabetes mellitus. All statistical tests were two-sided. During 927 995 person-years of follow-up, 316 participants developed pancreatic cancer. ABO blood type was associated with the risk of developing pancreatic cancer (P = .004; log-rank test). Compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted hazard ratios for incident pancreatic cancer were 1.32 [95% confidence interval {CI} = 1.02 to 1.72], 1.51 [95% CI = 1.02 to 2.23], and 1.72 [95% CI = 1.25 to 2.38], respectively). The association between blood type and pancreatic cancer risk was nearly identical in the two cohorts (P(interaction) = .97). Overall, 17% of the pancreatic cancer cases were attributable to inheriting a non-O blood group (blood group A, B, or AB). The age-adjusted incidence rates for pancreatic cancer per 100 000 person-years were 27 (95% CI = 23 to 33) for participants with blood type O, 36 (95% CI = 26 to 50) for those with blood type A, 41 (95% CI = 31 to 56) for those with blood type AB, and 46 (95% CI = 32 to 68) for those with blood type B. In two large, independent populations, ABO blood type was

  16. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  17. Mortality, Cancer, and Comorbidities Associated With Chronic Pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich Christian; Benfield, Thomas; Hyldstrup, Lars

    2014-01-01

    BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP). METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated...... cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic...... on a Danish nationwide cohort study, individuals with CP are at higher risk for death from cancer (particularly pancreatic cancer) and have a higher incidence of comorbidities than people without CP....

  18. Curcumin AntiCancer Studies in Pancreatic Cancer

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  19. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  20. Tea drinking and risk of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Junbao; Chen Long; Zhu Xiaodong

    2014-01-01

    Background Epidemiologic studies have reported inconsistent results regarding tea consumption and the risk of pancreatic cancer.This study aimed to investigate whether tea consumption is related to the risk of pancreatic cancer.Methods We searched Medline,EMBASE,ISI Web of Science,and the Cochrane library for studies published up to November 2013.We used a meta-analytic approach to estimate overall odds ratio (OR) and 95% confidence interval (CI) for the highest versus the lowest tea consumption categories.Results The summary OR for high versus no/almost never tea drinkers was 1.04 (95% CI:0.91-1.20),with no significant heterogeneity across studies (P=0.751;I2=0.0%).The OR was 0.99 (95% CI:0.77-1.28) in males and 1.01 (95% CI:0.79-1.29) in females.The OR was 1.07 (95% CI:0.85-1.34) in Asian studies,1.05 (95% CI:0.84-1.31) in European studies,and 0.98 (95% CI:0.72-1.34) in the US studies.The OR was 0.87 (95% CI:0.69-1.10) without adjustment for a history of diabetes and 1.16 (95% CI:0.97-0.39) after adjustment for a history of diabetes.The OR was 0.90 (95% CI:0.72-1.12) without adjustment for alcohol drinking and 1.16 (95% CI:0.96-1.39) after adjustment for alcohol drinking.The OR was 0.97 (95% CI:0.76-1.25) without adjustment for BMI and 1.07 (95% CI:0.87-1.31) after adjustment for BMI.Conclusion This systematic meta-analysis of cohort studies dose not provide quantitative evidence that tea consumption is appreciably related to the risk of pancreatic cancer,even at high doses.

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All Cancer Types ...

  2. Casein kinase II inhibition induces apoptosis in pancreatic cancer cells.

    Science.gov (United States)

    Hamacher, Rainer; Saur, Dieter; Fritsch, Ralph; Reichert, Maximilian; Schmid, Roland M; Schneider, Günter

    2007-09-01

    Pancreatic cancer is one of the most common causes of cancer death in western civilization. The five-year survival rate is below 1% and of the 10% of patients with resectable disease only around one-fifth survives 5 years. Survival rates have not changed much during the last 20 years, demonstrating the inefficacy of current available therapies. To improve the prognosis of pancreatic cancer, there is the need to develop effective non-surgical treatment for this disease. The protein kinase casein kinase II (CK2) is a ubiquitously expressed serine-threonine kinase and its activity is enhanced in all human tumors examined so far. The contribution of CK2 to the tumor maintenance of pancreatic cancer has not been investigated. To investigate the function of CK2 in pancreatic cancer cells we used the CK2 specific inhibitors 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole and Apigenin. Furthermore, we interfered with CK2 expression using CK2 specific siRNAs. Interfering with CK2 function led to a reduction of pancreatic cancer cell viability, which was due to caspase-dependent apoptosis. The induction of apoptosis correlated with a reduced NF-kappaB-dependent transcriptional activity. This study validates CK2 as a molecular drug target in a preclinical in vitro model of pancreatic cancer.

  3. Synchronous gallbladder and pancreatic cancer associated with pancreaticobiliary maljunction.

    Science.gov (United States)

    Rungsakulkij, Narongsak; Boonsakan, Paisarn

    2014-10-21

    We report the case of a 46-year-old woman who presented with chronic intermittent abdominal pain without jaundice; abdominal ultrasonography showed thickening of the gallbladder wall and dilatation of the bile duct. Endoscopic retrograde cholangiopancreaticography showed pancreatobiliary maljunction with proximal common bile duct dilatation. Pancreatobiliary maljunction was diagnosed. A computed tomography scan of the abdomen showed suspected gallbladder cancer and distal common bile duct obstruction. A pancreatic head mass was incidentally found intraoperative. Radical cholecystectomy with pancreatoduodenectomy was performed. The pathological report showed gallbladder cancer that was synchronous with pancreatic head cancer. In the pancreatobiliary maljunction with pancreatobiliary reflux condition, double primary cancer of the pancreatobiliary system should be awared.

  4. Screening and surveillance approaches in familial pancreatic cancer.

    Science.gov (United States)

    Canto, Marcia Irene

    2008-07-01

    Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.

  5. Cancer Clusters

    Science.gov (United States)

    ... Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  6. Is Type 2 Diabetes a Risk Factor for Pancreatic Cancer?

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2009-11-01

    Full Text Available The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long time. Taking into consideration diabetes mellitus irrespective of type, there is a lack of agreement regarding the data; in fact, some epidemiological studies have excluded this possibility whereas others have found a relationship between the presence of diabetes and the development of pancreatic cancer. On the other hand, a recent study has reported that metformin may have a protective effect on the development of pancreatic cancer [1]. Therefore, we would briefly revise the data both for and against the possibility that pancreatic cancer is a consequence of long-standing diabetes.

  7. Obesity adversely affects survival in pancreatic cancer patients.

    Science.gov (United States)

    McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A; Kim, George P; Halfdanarson, Thorvardur R; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R

    2010-11-01

    Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self-reported diabetes and fasting blood glucose in the survival model. BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], Ppancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Copyright © 2010 American Cancer Society.

  8. Pancreatic cancer in obesity: epidemiology, clinical observations, and basic mechanisms.

    Science.gov (United States)

    Zyromski, Nicholas J; White, Patrick B

    2011-06-01

    Obesity, now a worldwide epidemic, causes myriad medical problems. One of the most significant obesity-related problems is the well-recognized relationship between obesity and various malignancies, including pancreatic cancer. Pancreatic cancer is a devastating disease--the annual death rate nearly approximates its incidence. While surgical extirpation provides the best chance at long term survival, systemic therapy is largely ineffective: even those patients undergoing successful operative resection have only approximately 20% 5-year survival. These poor outcomes are largely a consequence of poor understanding of tumor biology. Clearly, identification of novel treatment strategies is of paramount importance; investigation of pancreatic cancer biology from the novel aspect of obesity offers the potential to identify unique therapeutic targets. This manuscript reviews the epidemiology, clinical findings, and putative basic science mechanisms underlying obesity-related pancreatic cancer.

  9. Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer

    Science.gov (United States)

    A summary of results from a phase III trial that compared the combination of albumin-bound paclitaxel (nab-paclitaxel [Abraxane®]) and gemcitabine (Gemzar®) versus gemcitabine alone in patients with metastatic pancreatic cancer.

  10. [Borderline resectable pancreatic cancer - a definition and effective treatment strategy].

    Science.gov (United States)

    Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Sugawara, Gen; Takahashi, Yuh; Kokuryo, Toshio; Tsunoda, Nobuyuki; Fukaya, Masahide; Uehara, Keisuke; Itatsu, Keita; Yoshioka, Yuichiro; Nagino, Masato

    2012-03-01

    The survival benefit of extended surgery for advanced pancreatic cancer has been denied by four randomized controlled trials. However, there still is confusion and conflict over the definition and effective treatment strategy for so-called locally advanced or borderline resectable pancreatic cancer. Although there are a number of reports that showed outcomes of preoperative chemotherapy or chemoradiotherapy for this disease, the definitions and treatment regimens described in these studies vary. Moreover, all of the studies were Phase I / II trials or retrospective analysis, and there is no Phase III trial currently focused on this issue. It is urgently necessary to establish an international consensus on the definition of borderline resectable pancreatic cancer. The usefulness of neoadjuvant treatment for this disease should also be elucidated in future clinical trials. In this review article, we discuss the current understanding and definition of borderline resectable pancreatic cancer, and the value of neoadjuvant treatment strategy for treating it.

  11. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  12. Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Dongping Wei

    2015-02-01

    Full Text Available In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1, an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.

  13. Is Type 2 Diabetes a Risk Factor for Pancreatic Cancer?

    OpenAIRE

    Raffaele Pezzilli; Antonio Maria Morselli-Labate; Riccardo Casadei

    2009-01-01

    The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long time. Taking into consideration diabetes mellitus irrespective of type, there is a lack of agreement regarding the data; in fact, some epidemiological studies have excluded this possibility whereas others have found a relationship between the presence of diabetes and the development of pancreatic cancer. On the other hand, a recent study has reported that metformin may have a pro...

  14. Value of ultrasound examination in differential diagnosis of pancreatic lymphoma and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Li Qiu; Yan Luo; Yu-Lan Peng

    2008-01-01

    AIM:To investigate the value of clinical manifestations and ultrasound examination in the differential diagnosis of pancreatic lymphoma and pancreatic cancer.METHODS:The clinical and ultrasonic characteristics of 12 cases of pancreatic lymphoma and 30 cases of pancreatic cancer were retrospectively analyzed.RESULTS:Statistically significant differences were found in the course of disease,back pain,jaundice,carcino-embryonic antigen (CEA) and CA19-9 increase,palpable abdominal lump,superficial lymph node enlargement,fever and night sweats,lesion size,bile duct expansion,pancreatic duct expansion,vascular involvement,retroperitoneal (below the renal vein level)lymph node enlargement,and intrahepatic metastasis between pancreatic lymphoma and pancreatic cancer.There were no significant differences in age of onset,gender ratio,weight loss,nausea and vomiting,lesion position,the echo of the lesion,and the blood flow of the lesion.CONCLUSION:Pancreatic lymphoma should be considered for patients with long lasting symptoms,superficial lymph node enlargement,palpable abdominal lump,fever and night sweats,relatively large lesions,and retroperitoneal (below the level of the renal vein) lymph node enlargement.A diagnosis of pancreatic cancer should be considered more likely in the patients with relatively short disease course,jaundice,back pain,CEA and CA19-9 increase,relatively small lesions,bile duct expansion,obvious pancreatic duct expansion,peripheral vascular wrapping and involvement,or intrahepatic metastases.

  15. MicroRNA-gene signaling pathways in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Alexandra Drakaki

    2013-10-01

    Full Text Available Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.

  16. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  17. Organoid models of human and mouse ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  18. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  19. Organoid models of human and mouse ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  20. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  1. Depression and Pancreatic Cancer: A Poorly Understood Link

    Directory of Open Access Journals (Sweden)

    Nektaria Makrilia

    2009-01-01

    Full Text Available Although pancreatic carcinoma and depression have been linked for many years, the prevalence and relationship of these two entities are still poorly understood. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. If the definition of depression is broadened to include mild depression in addition to major depression, these numbers may increase. Depression in pancreatic cancer is a condition that must be diagnosed and treated, as studies have shown that depression is a detrimental factor in the last stages of life of cancer patients as patients with high score of depression have worse survival rates in breast and hepatobiliary cancers. Treatment for depression has also been shown to impact quality of life and may bring increased comfort during end of life. This article reviews the literature linking pancreatic carcinoma to depression as well as the appropriate therapeutic approach. In addition, for the first time, it fully underlines the key role of a social worker as a key participant throughout the cancer continuum: at time of diagnosis, treatment, relapse, survivorship, end of life and bereavement in the management of pancreatic cancer patients.

  2. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  3. Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis.

    Science.gov (United States)

    Lu, Pei-Ying; Shu, Long; Shen, Shan-Shan; Chen, Xu-Jiao; Zhang, Xiao-Yan

    2017-01-05

    A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77-0.95; p = 0.004) and light-moderate drinking patterns (OR = 0.90; 95% CI: 0.83-0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06-1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10-1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light-moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings.

  4. Top classic citations in pancreatic cancer research.

    Science.gov (United States)

    Li, Qiang; Jiang, Yuan

    2016-11-29

    The number of times that articles are cited by is widely used to evaluate the impact of an article or an individual author has on its scientific community. This bibliometric analysis aimed to explore the top classic citations in pancreatic cancer (PC) research. A computerized literature search was conducted using the database, the Science Citation Index Expanded. The top 100 highly cited articles were included and further analyzed. The most cited article had 3,032 citations, with a mean of 626 citations per paper. These highly cited articles were published in 37 journals, led by Cancer Research (15 articles). Of the 100 articles, 40 were observational studies, 36 dealt with basic science, and 14 were randomized controlled trials. These articles came from 11 countries, with the USA contributing 79 articles. Fifty-one institutions produced these 100 citation classics, led by Johns Hopkins University (20 articles). Twenty-seven persons authored two or more of the top-cited articles, led by Kern SE (6) and Yeo CJ (5). This analysis of the top highly cited articles allows for the recognition of major advances in PC research and gives a historic perspective on the progress of this specialty of PC research.

  5. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Gukovsky, Ilya; Li, Ning; Todoric, Jelena; Gukovskaya, Anna; Karin, Michael

    2013-06-01

    Inflammation and autophagy are cellular defense mechanisms. When these processes are deregulated (deficient or overactivated) they produce pathologic effects, such as oxidative stress, metabolic impairments, and cell death. Unresolved inflammation and disrupted regulation of autophagy are common features of pancreatitis and pancreatic cancer. Furthermore, obesity, a risk factor for pancreatitis and pancreatic cancer, promotes inflammation and inhibits or deregulates autophagy, creating an environment that facilitates the induction and progression of pancreatic diseases. However, little is known about how inflammation, autophagy, and obesity interact to promote exocrine pancreatic disorders. We review the roles of inflammation and autophagy, and their deregulation by obesity, in pancreatic diseases. We discuss the connections among disordered pathways and important areas for future research. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Anthropometric Measures, Body Mass Index and Pancreatic Cancer: a Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Arslan, Alan A.; Helzlsouer, Kathy J.; Kooperberg, Charles; Shu, Xiao-Ou; Steplowski, Emily; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gross, Myron D.; Jacobs, Eric J.; LaCroix, Andrea Z.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael Z.; Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Bamlet, William R.; Barricarte, Aurelio; Bingham, Sheila A.; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Chanock, Stephen J.; Clipp, Sandra; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kraft, Peter; Lynch, Shannon M.; Manjer, Jonas; Manson, JoAnn E.; McTiernan, Anne; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Palli, Domenico; Rohan, Thomas E.; Slimani, Nadia; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Patel, Alpa V.

    2010-01-01

    Background Pooled data were analyzed from the NCI Pancreatic Cancer Cohort Consortium (PanScan) to study the association between pre-diagnostic anthropometric measures and risk of pancreatic cancer. Methods PanScan applied a nested case-control study design and included 2,170 cases and 2,209 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI), weight, height, waist circumference, and waist-to-hip ratio (WHR), as well as conventional BMI categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (30.0-34.9 kg/m2), and severely obese (≥35.0 kg/m2). Models were adjusted for potential confounders. Results Among all subjects, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs. lowest BMI quartile = 1.33, 95% CI = 1.12-1.58, Ptrend < 0.001). Among men, the adjusted OR for pancreatic cancer for the highest vs. lowest quartile of BMI was 1.33 (95% CI = 1.04-1.69, Ptrend <0.03). Among women, the adjusted OR for pancreatic cancer for the highest quartile of BMI was 1.34 (95% CI = 1.05-1.70, Ptrend = 0.01). Increased WHR was associated with increased risk of pancreatic cancer among women (adjusted OR for the highest vs. lowest quartile = 1.87, 95% CI = 1.31-2.69, Ptrend = 0.003) but less so in men. Conclusion The findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. PMID:20458087

  7. Expression levels of microRNA-375 in pancreatic cancer.

    Science.gov (United States)

    Song, Shiduo; Zhou, Jian; He, Songbing; Zhu, Dongming; Zhang, Zixiang; Zhao, Hua; Wang, Yi; Li, Dechun

    2013-05-01

    MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin that have been increasingly shown to have altered expressions in various cancer types. The expression levels of miR-375 have not been comprehensively investigated in pancreatic cancer. In this study, total RNA was extracted from 44 pairs of pancreatic cancer tissues and non-tumor adjacent tissues, as well as from four pancreatic cancer cell lines, Panc-1, SW1990, BxpC3 and Patu8988. Following polyadenylation and reverse transcription, the expression levels of miR-375 were determined by real-time PCR and the difference in expression was calculated using the 2(-ΔΔCt) method. The correlation between the expression levels of miR-375 and clinicopathological characteristics of pancreatic cancer was also assessed. miR-375 expression was frequently downregulated in the pancreatic cancer tissues compared to their non-tumor counterparts (PBxPC3, P=0.018; Patu8988, P=0.017; paired t-test). However, no significant correlations were observed between the low expression of miR-375 and parameters including gender, age, tumor size, tumor location and histological grade (P>0.05). The low expression of miR-375 was correlated with pT stage, lymph node metastases and pTNM stage (P<0.05) (non-parametric test; Mann-Whitney U test between 2 groups and Kruskal-Wallis H test for ≥3 groups). In conclusion, miR-375 is potentially involved in the carcinogenesis of pancreatic cancers and serves as is a potential biomarker for pancreatic cancer.

  8. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr

  9. Regulators of epithelial mesenchymal transition in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Shin eHamada

    2012-07-01

    Full Text Available Pancreatic cancer is a leading cause of cancer related death due to its invasive nature. Despite the improvement of diagnostic strategy, early diagnosis of pancreatic cancer is still challenging. Surgical resection is the only curative therapy, while vast majority of patients are not eligible for this therapeutic option. Complex biological processes are involved in the establishment of invasion and metastasis of pancreatic cancer and epithelial-mesenchymal transition (EMT has been reported to play crucial role. EMT is part of the normal developmental processes which mobilizes epithelial cells and yields mesenchymal phenotype. Deregulation of EMT inducing molecules in pancreatic cancer is reported, such as multiple cytokines, growth factors and downstream transcriptional factors. In addition to these molecules, non-coding RNA including miRNA also contributes to EMT. EMT of cancer cell also correlates with cancer stem cell properties such as chemoresistance or tumorigenicity, therefore these upstream regulators of EMT could be attractive therapeutic targets and several candidates are examined for clinical application. This review summarizes recent advances in this field, focusing the regulatory molecules of EMT and their downstream targets. Further understanding and research advances will clarify the cryptic mechanism of cancer metastasis and delineate novel therapeutic targets.

  10. Laparoscopic versus open distal pancreatectomy for pancreatic cancer

    NARCIS (Netherlands)

    Riviere, D.M.; Gurusamy, K.S.; Kooby, D.A.; Vollmer, C.M.; Besselink, M.G.; Davidson, B.R.; Laarhoven, C.J.H.M. van

    2016-01-01

    BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In

  11. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr

  12. Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic cancer:15-year experience

    Institute of Scientific and Technical Information of China (English)

    De-Qing Mu; You-Shu Peng; Qiao-Jian Xu

    2004-01-01

    AIM: To summarize progress in the study of K-ras gene studies in pancreatic cancer and its potential clinical significance in screening test for early detection of pancreatic cancer, and to differentiate pancreatic cancer from chronic pancreatitis in recent decade.METHODS: Literature search (MEDLINE 1986-2003) was performed using the key words K-ras gene, pancreatic cancer, chronic pancreatitis, and diagnosis. Two kind of opposite points of view on the significance of K-ras gene in detection early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis were investigated.The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of pancreatic cancers, and is not rare in patients with chronic pancreatitis, and represents an increased risk of developing pancreatic cancer. However, the significance of the detection of this mutation in specimens obtained by needle aspiration from pure pancreatic juice and from stools for its utilization for the detection of early pancreatic cancer, and differentiation pancreatic cancer from chronic pancreatitis remains controversial. CONCLUSION: The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertains in clinical pratice. Nevertheless, K-ras mutation screening may increase the sensitivity of FNA and ERP cytology and may be useful in identifying pancreatitis patients at high risk for developing cancer, and as a adjunct with cytology to differentiate pancreatic cancer from chronic pancreatitis.

  13. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ethan V Abel

    Full Text Available Pancreatic cancer stem cells (CSCs represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized.Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth.Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population.The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.

  14. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    Science.gov (United States)

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  15. STAT3 as an emerging molecular target in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Sharma NK

    2014-08-01

    Full Text Available Narinder Kumar Sharma,1 Sharmila Shankar,2 Rakesh K Srivastava1 1Department of Pharmacology, Toxicology and Therapeutics, and Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Kansas City VA Medical Center, Kansas City, MO, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer related deaths. Although, surgical resection of pancreatic cancer may provide the best chance for cure and long-term survival, due to the late onset of symptoms only 15% to 20% of patients have resectable tumors. Most of the pancreatic tumors have mutations in the K-ras gene, followed by mutations in tumor suppressor genes such as p53 and SMAD4. In addition, there is growing evidence for the potential involvement of signal transducer and activator of transcription 3 (STAT3 in malignant transformation of pancreatic cancer. STAT3 plays critical roles in regulating many physiological functions in normal and malignant tissues, such as inflammation, survival, proliferation, differentiation, and angiogenesis. STAT3 is activated by a wide variety of cytokines, growth factors, and other stimuli. Unlike other members of the STAT family, ablation of STAT3 leads to embryonic lethality and conditional loss of STAT3 protein in adult tissues, leading to a variety of abnormalities, confirming that STAT3 participates in a wide variety of physiological processes. Constitutive activation of STAT3 is implicated in a wide range of human cancers; therefore, STAT3 has been identified as a novel target to treat and prevent cancers. Several STAT3 inhibitors display antitumor effectiveness, and data supporting the use of STAT3 inhibitors are emerging. Different approaches used for the inhibition of activated STAT3 include modulating upstream positive or negative regulators or directly targeting its different domains. These approaches have been used in the inhibition of STAT3 in different cancers, but in this review, we will focus specifically on the inhibition

  16. Prognostic value of PDL1 expression in pancreatic cancer.

    Science.gov (United States)

    Birnbaum, David J; Finetti, Pascal; Lopresti, Alexia; Gilabert, Marine; Poizat, Flora; Turrini, Olivier; Raoul, Jean-Luc; Delpero, Jean-Robert; Moutardier, Vincent; Birnbaum, Daniel; Mamessier, Emilie; Bertucci, François

    2016-11-01

    Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.

  17. Control of Apoptosis in Treatment and Biology of Pancreatic Cancer.

    Science.gov (United States)

    Modi, Shrey; Kir, Devika; Banerjee, Sulagna; Saluja, Ashok

    2016-02-01

    Pancreatic cancer is estimated to be the 12th most common cancer in the United States in 2014 and yet this malignancy is the fourth leading cause of cancer-related death in the United States. Late detection and resistance to therapy are the major causes for its dismal prognosis. Apoptosis is an actively orchestrated cell death mechanism that serves to maintain tissue homoeostasis. Cancer develops from normal cells by accruing significant changes through one or more mechanisms, leading to DNA damage and mutations, which in a normal cell would induce this programmed cell death pathway. As a result, evasion of apoptosis is one of the hallmarks of cancer cells. PDAC is notoriously resistant to apoptosis, thereby explaining its aggressive nature and resistance to conventional treatment modalities. The current review is focus on understanding different intrinsic and extrinsic pathways in pancreatic cancer that may affect apoptosis in this disease.

  18. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

    2015-07-17

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

  19. Contribution of environment and genetics to pancreatic cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Barbara A Hocevar

    Full Text Available Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00 ± 0.05 versus both healthy unrelated and related controls (0.70 ± 0.06, pA and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.

  20. Risk Factors for Pancreatic Cancer in China: A Multicenter Case-Control Study

    OpenAIRE

    Zhaoxu Zheng

    2016-01-01

    Background: Despite having one of the highest mortality rates of all cancers, the risk factors of pancreatic cancer remain unclear. We assessed risk factors of pancreatic cancer in China. Methods: A case-control study design was conducted using data from four hospital-based cancer registries (Henan Provincial Cancer Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences). Controls were equally matched and selected fro...

  1. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  2. Neural Invasion in Pancreatic Cancer: The Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Demir, Ihsan Ekin; Ceyhan, Güralp O.; Liebl, Florian; D’Haese, Jan G.; Maak, Matthias; Friess, Helmut, E-mail: friess@chir.med.tu-muenchen.de [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

    2010-07-14

    In the past 15 years, invasion of nerves by cancer cells has escaped from its role as a mere bystander in cancer biology and turned into an attractive niche to study the heterotypic interaction between cancer cells and neurons. Today, neural invasion (NI) in pancreatic cancer (PCa) stands out due to the recent demonstration of its association with tumor progression, local recurrence and neuropathic pain. Accordingly, recent research on NI in PCa revealed the critical involvement of numerous nerve- or cancer cell-derived molecules in several novel in vitro and in vivo models of NI, which, however, still need further major improvement.

  3. Enteric duplication cyst of the pancreas associated with chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Chiu, Alexander S; Bluhm, David; Xiao, Shu-Yan; Waxman, Irving; Matthews, Jeffrey B

    2014-05-01

    Pancreas-associated enteric duplication cysts are rare developmental anomalies that communicate with the main pancreatic duct and may be associated with recurrent acute and chronic abdominal pain in children. In adults, these lesions may masquerade as pancreatic pseudocysts or pancreatic cystic neoplasms. An adult patient with a pancreas-associated enteric duplication is described which represents the first reported instance of association with both chronic calcific pancreatitis and pancreatic cancer. The clinical spectrum of pancreas-associated enteric duplication cyst, including diagnostic and therapeutic options, is reviewed.

  4. Islet Inflammation: A Causal Link Between Diabetes and Pancreatic Cancer?

    Directory of Open Access Journals (Sweden)

    Peter Butler

    2014-09-01

    Full Text Available Type 2 diabetes (T2DM is characterized hyperglycemia due to impaired insulin secretion and a deficit of pancreatic beta cells in the setting of insulin resistance. Most individuals are able to compensate for insulin resistance by increasing insulin secretion so the genetic basis of T2DM appears to be linked to the underlying mechanisms leading to this abnormal pancreatic islet response to insulin resistance. In support of this, pancreatic islets in T2DM have a specific pathology. The ~65% deficit in beta cells is presumably due to increased beta cell apoptosis, the underlying mechanisms of which include a misfolded protein induced endoplasmic reticulum stress, mitochondrial dysfunction and local release of inflammatory cytokines. It has long been recognized that there is an association between T2DM and pancreatic cancer. One explanation for this is the development of diabetes in relation to pancreatic cancer, when the diagnoses are temporarily related.

  5. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  6. Diagnosis of pancreatic cancer by cytology and telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopy

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Jie-Fei Huang; Hong Zhang; Jian-Ping Chen

    2007-01-01

    BACKGROUND:Telomerase activity is reported to be speciifc and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS:Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat ampliifcation protocol assay (PCR-TRAP-ELISA). RESULTS:D450 values of telomerase activity were 0.446± 0.2700 in pancreatic cancer and 0.041±0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7%(12/18) of the patients. CONCLUSIONS:Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.

  7. Road map for pain management in pancreatic cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Marie José Lahoud; Hampig Raphael Kourie; Joelle Antoun; Lana El Osta; Marwan Ghosn

    2016-01-01

    Beside its poor prognosis and its late diagnosis, pancreatic cancer remains one of the most painful malignancies. Optimal management of pain in this cancer represents a real challenge for the oncologist whose objective is to ensure a better quality of life to his patients. We aimed in this paper to review all the treatment modalities incriminated in the management of pain in pancreatic cancer going from painkillers, chemotherapy, radiation therapy and interventional techniques to agents under investigation and alternative medicine. Although specific guidelines and recommendations for pain management in pancreatic cancer are still absent, we present all the possible pain treatments, with a progression from medical multimodal treatment to radiotherapy and chemotherapy then interventional techniques in case of resistance. In addition, alternative methods such as acupuncture and hypnosis can be added at any stage and seems to contribute to pain relief.

  8. Acute Recurrent Pancreatitis: A Possible Clinical Manifestation of Ampullary Cancer

    Directory of Open Access Journals (Sweden)

    Athanasios Petrou

    2011-11-01

    Full Text Available Context Acute recurrent pancreatitis still poses diagnostic difficulties. The coexistence or moreover the causative relationship of carcinoma of the ampulla of Vater and acute recurrent pancreatitis is fairly rare. Case report We present a case of carcinoma of the ampulla of Vater that presented with acute recurrent necrotizing pancreatitis complicated with pseudocysts. A diagnosis of malignancy in the ampulla was only made after several ERCP attempts due to residual inflammation at the periampullary area. Conclusion Malignancy at the ampulla of Vater causing recurrent episodes of pancreatitis represents a realistic risk and attempts to diagnose the underlying cause should always take into account the possibility of cancer.

  9. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    Science.gov (United States)

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  10. Pancreatic cancer mortality in China (1991-2000)

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Gong-Huan Yang; Xing-Hua Lu; Zheng-Jing Huang; Hui Li

    2003-01-01

    AIM: To describe the mortality rate of pancreatic cancer and its distribution in China during the period of 1991-2000.METHODS: Based on the data of demography and death collected through China′s Disease Surveillance Point System (DSPS) over the period of 1991-2000, the distribution of death rate of pancreatic cancer was described in terms of age group, gender, calendar year, rural/urban residence and administrative district.RESULTS: A total of 1 619 death cases attributed to pancreatic cancer (975 men and 644 women) were reported by DSPS during 1991-2000. The reported, adjusted and agestandardized mortality rates increased from 1.46, 1.75, and 2.18 per 100 000 populations in 1991 to 2.38, 3.06, and 3.26per 100 000 populations in 2000. The majority (69.62 %) of the deaths of pancreatic cancer were seen in the age group of 60 years and older. The mortality rate was higher in men than in women, but the male to female death rate ratios decreased during the 10 years. Our data also showed that the death rate of pancreatic cancer in urban areas was about 2-4 fold higher than that in rural areas, and in Northeast and East China, the death rates were higher than those in the other 5 administrative districts.CONCLUSION: The death rate due to pancreatic cancer was rising during the period of 1991-2000 and the peak mortality of pancreatic cancer might arrive in China.

  11. Risk Factors for Pancreatic Cancer in China: A Multicenter Case-Control Study.

    Science.gov (United States)

    Zheng, Zhaoxu; Zheng, Rongshou; He, Yutong; Sun, Xibin; Wang, Ning; Chen, Tianhui; Chen, Wanqing

    2016-01-01

    Despite having one of the highest mortality rates of all cancers, the risk factors of pancreatic cancer remain unclear. We assessed risk factors of pancreatic cancer in China. A case-control study design was conducted using data from four hospital-based cancer registries (Henan Provincial Cancer Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences). Controls were equally matched and selected from family members of non-pancreatic cancer patients in the same hospitals. Face-to-face interviews were conducted by trained staff using questionnaires. Conditional logistic regression models were used to assess odd ratios (ORs) and 95% confident intervals (CIs). Among 646 recruited participants, 323 were pancreatic cancer patients and 323 were controls. Multivariate logistic analysis suggested that pancreatic cancer family history (adjusted OR 1.23; 95% CI, 1.11-3.70), obesity (adjusted OR 1.77; 95% CI, 1.22-2.57), diabetes (adjusted OR 2.96; 95% CI, 1.48-5.92) and smoking (adjusted OR 1.78; 95% CI, 1.02-3.10) were risk factors for pancreatic cancer, but that drinking tea (adjusted OR 0.49; 95% CI, 0.25-0.84) was associated with reduced risk of pancreatic cancer. Cigarette smoking, family history, obesity, and diabetes are risk factors of pancreatic cancer, which is important information for designing early intervention and preventive strategies for pancreatic cancer and may be beneficial to pancreatic cancer control in China.

  12. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer risk

  13. Developing a multicenter cooperative research system for pancreatic cancer in China

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu-pei

    2007-01-01

    @@ Pancreatic cancer often starts silently without symptoms at its early stage but progresses quite rapidly and has a poor prognosis. In recent years the incidence of pancreatic cancer has been rising year by year.1

  14. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer

  15. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy.

    Science.gov (United States)

    Wang, Zhiwei; Ahmad, Aamir; Li, Yiwei; Azmi, Asfar S; Miele, Lucio; Sarkar, Fazlul H

    2011-04-01

    Pancreatic cancer is the most aggressive malignant disease once it is diagnosed and it remains the fourth leading cause of cancer-related death in the U.S.A. Recent data indicates that the Notch signaling pathway plays an important role in the development and progression of pancreatic cancer. Emerging evidence also suggests that the activation of the Notch signaling pathway is mechanistically associated with molecular characteristics of cancer stem cells (CSCs) in pancreatic cancer. Moreover, CSCs are known to be highly drug-resistant, suggesting that targeted inactivation of Notch signaling would be useful for overcoming drug resistance and the elimination of CSCs. This review describes the roles of the Notch signaling pathway in pancreatic cancer with a special emphasis on its novel functions in the regulation of pancreatic CSC. Moreover, the review also proposes that targeting the Notch signaling pathway by natural agents may represent a novel strategy for overcoming drug resistance and the elimination of CSCs, which would be useful for the successful treatment of patients diagnosed with pancreatic cancer.

  16. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies

    Directory of Open Access Journals (Sweden)

    Chiorean EG

    2015-07-01

    Full Text Available Elena Gabriela Chiorean, Andrew L Coveler Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%, CDK2NA (90%, TP53 (75%–90%, DPC4/SMAD4 (50%. In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of

  17. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

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    Manju D. Chandrasegaram

    2013-01-01

    Full Text Available Background. Autoimmune pancreatitis (AIP often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS- guided fine-needle aspiration (FNA of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP.

  18. Second line treatment options for pancreatic cancer.

    Science.gov (United States)

    Passero, Frank C; Saif, Muhammad Wasif

    2017-08-18

    ABTRACT Introduction: Patients with advanced pancreatic cancer (APC) refractory to first-line therapy have a dismal prognosis and limited therapeutic options, with only one option consisting of nanoliposomal irinotecan in combination with fluorouracil and folinic acid which was approved by FDA based upon results of the phase III NAPOLI-1 study. Areas covered: We performed a literature search for relevant published clinical trials, abstracts of trials in progress and ongoing or planned trials for the second line treatment of APC using Pubmed.com, ClinicalTrials.gov and American Society of Clinical Oncology (ASCO) abstract search as sources. We present an in-depth analysis of the phase I-III clinical trials determining the role and efficacy of second-line treatment in patients with APC. We also describe ongoing studies and rationale for future investigation. Expert opinion: Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and FOLFIRINOX in APC, median overall survival remains less than 12 months, highlighting the need to develop second-line therapies. In order to establish much needed effective second-line treatment options, we need cooperative efforts among institutions and community practices in enrolling these refractory patients in clinical trials. It should be emphasized that in addition to chemotherapy options, all patients should have the opportunity to consult with nutritionist, social worker and palliative care health providers to assist with goals of care, symptom management and end of life discussions.

  19. Cadmium Exposure and Pancreatic Cancer in South Louisiana

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    Brian G. Luckett

    2012-01-01

    Full Text Available Cadmium has been hypothesized to be a pancreatic carcinogen. We test the hypothesis that cadmium exposure is a risk factor for pancreatic cancer with a population-based case-control study sampled from a population with persistently high rates of pancreatic cancer (south Louisiana. We tested potential dietary and nondietary sources of cadmium for their association with urinary cadmium concentrations which reflect long-term exposure to cadmium due to the accumulation of cadmium in the kidney cortex. Increasing urinary cadmium concentrations were significantly associated with an increasing risk of pancreatic cancer (2nd quartile OR = 3.34, 3rd = 5.58, 4th = 7.70; test for trend P≤0.0001. Potential sources of cadmium exposure, as documented in the scientific literature, found to be statistically significantly associated with increased risk of pancreatic cancer included working as a plumber, pipefitter or welder (OR = 5.88 and high consumption levels of red meat (4th quartile OR = 6.18 and grains (4th quartile OR = 3.38. Current cigarette smoking, at least 80 pack years of smoking, occupational exposure to cadmium and paints, working in a shipyard, and high consumption of grains were found to be statistically significantly associated with increased concentrations of urinary cadmium. This study provides epidemiologic evidence that cadmium is a potential human pancreatic carcinogen.

  20. Fascin promotes the motility and invasiveness of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Feng Xu; Shuang-Ni Yu; Zhao-Hui Lu; Jian-Ping Liu; Jie Chen

    2011-01-01

    AIM: To explore the role of actin-bundling protein, fascin during the progression of pancreatic cancer. METHODS: The plasmid expressing human fascin-1 was stably transfected into the pancreatic cancer cell line MIA PaCa-2. The proliferation, cell cycle, motility, scattering, invasiveness and organization of the actin filament system in fascin-transfected MIA PaCa-2 cells and control non-transfected cells were determined. RESULTS: Heterogeneous overexpression of fascin markedly enhanced the motility, scattering, and invasiveness of MIA PaCa-2 cells. However, overexpression of fascin had minimal effect on MIA PaCa-2 cell proliferation and cell cycle. In addition, cell morphology and organization of the actin filament system were distinctly altered in fascin overexpressed cells. When transplanted into BALB/c-nu mice, fascin-transfected pancreatic cancer cells developed solid tumors at a slightly slower rate, but these tumors displayed more aggressive behavior in comparison with control tumors. CONCLUSION: Fascin promotes pancreatic cancer cell migration, invasion and scattering, thus contributes to the aggressive behavior of pancreatic cancer cells.

  1. Survivin expression and its clinical significance in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Lee Kyung Shik

    2005-10-01

    Full Text Available Abstract Background Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor. Methods We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record. Results Of the 49 cases of pancreatic cancer, 46 cases (93.9% were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively. Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression. Conclusion Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.

  2. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  3. Advances in early diagnosis and therapy of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Xu; Tai-Ping Zhang; Yu-Pei Zhao

    2011-01-01

    BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA  SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articleswerefromCHKD(ChinaHospitalKnowledgeDatabase). RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients. Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine-based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

  4. Inositol hexaphosphate (IP6): a novel treatment for pancreatic cancer.

    Science.gov (United States)

    Somasundar, Ponnandai; Riggs, Dale R; Jackson, Barbara J; Cunningham, Cynthia; Vona-Davis, Linda; McFadden, David W

    2005-06-15

    Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors including breast and colon. The effects of IP6 have not been evaluated in pancreatic cancer. We hypothesized that IP6 would significantly inhibit cell growth and increase the apoptotic rate of pancreatic cancer in vitro. Two pancreatic cancer cell lines (MIAPACA and PANC1) were cultured using standard techniques and treated with IP6 at doses of 0.5, 1.0, and 5.0 mm. Cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated by Annexin V-FITC and results calculated using FACS analysis. Statistical analysis was performed by ANOVA. Significant reductions (P IP6 concentrations tested in both cell lines and at both time points. Reductions in cell proliferation ranged from 37.1 to 91.5%. IP6 increased early and late apoptotic activity (P IP6 significantly decreased cellular growth and increased apoptosis. Our findings suggest that IP6 has the potential to become an effective adjunct for pancreatic cancer treatment. Further in vivo and human studies are needed to evaluate safety and clinical utility of this agent in patients with pancreatic cancer.

  5. Potentials of interferon therapy in the treatment of pancreatic cancer.

    Science.gov (United States)

    Booy, Stephanie; Hofland, Leo; van Eijck, Casper

    2015-05-01

    Pancreatic cancer is a highly aggressive malignancy with limited treatment options. To improve survival for patients with pancreatic cancer, research has focused on other treatment modalities like adding biological modulators such as type-I interferons (IFNs). Type I IFNs (ie, IFN-α/IFN-β) have antiproliferative, antiviral, and immunoregulatory activities. Furthermore, they are able to induce apoptosis, exert cell cycle blocking, and sensitize tumor cells for chemo- and radiotherapy. A few years ago in vitro, in vivo, and several clinical trials have been described regarding adjuvant IFN-α therapy in the treatment of pancreatic cancer. Some studies reported a remarkable increase in the 2- and 5-year survival. Unfortunately, the only randomized clinical trial did not show a significant increase in overall survival, although the increased median survival implicated that some patients in the experimental group benefited from the adjuvant IFN-α therapy. Furthermore, encouraging in vitro and in vivo data points to a possible role for adjuvant IFN therapy. However, up till now, the use of IFNs in the treatment of pancreatic cancer remains controversial. This review, therefore, aims to describe, based on the available data, whether there is a distinct role for IFN therapy in the treatment of pancreatic cancer.

  6. Revising You the Staging for Pancreatic Cancer in 2012

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2012-03-01

    Full Text Available In 2010, there were an estimated 43,140 new cases of pancreatic ductal adenocarcinoma and 36,800 deaths from pancreatic cancer in the United States [1]. This represents the 10th most common cancer diagnosis but the 4th most common cause of cancer-related death among men and women (6% of all cancer-related deaths, highlighting the disproportionate mortality associated with this diagnosis [2]. Why is Staging so Important? Sadly, only 20% patients are “resectable” at the time of diagnosis [3]. Pancreatic cancer is “resectable” if the tumor is confined to the pancreas without the encasement of adjacent surrounding major vessels, or distant metastases. Even among those patients who undergo resection for pancreatic cancer and have tumor-free margins, the 5-year survival rate after resection is 10-25% and the median survival is 15-19 months [3]. “Locally advanced pancreatic cancer” is defined as the tumor that has a local invasion: arterial (celiac trunk, hepatic artery, superior mesenteric artery or venous (portal vein, superior mesenteric vein but not metastasized, and represents about 25% of pancreatic cancer cases at presentation [4]. Locally advanced stage is associated with a median survival of 6-10 months. The vast majority of these patients develop metastatic disease within the first year of therapy. The tumor is considered “advanced” when it has metastasized to other organs, such as the liver or distant areas of the abdomen. Approximately 45% to 55% of patients are diagnosed at this stage. The prognosis of patients with advanced disease remains extremely poor, with a median survival of 6 months [5].

  7. The WSB1 gene is involved in pancreatic cancer progression.

    Directory of Open Access Journals (Sweden)

    Cendrine Archange

    Full Text Available BACKGROUND: Pancreatic cancer cells generate metastases because they can survive the stress imposed by the new environment of the host tissue. To mimic this process, pancreatic cancer cells which are not stressed in standard culture conditions are injected into nude mice. Because they develop xenografts, they should have developed adequate stress response. Characterizing that response might provide new strategies to interfere with pancreatic cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: In the human pancreatic cancer cell lines Panc-1, Mia-PaCa2, Capan-1, Capan-2 and BxPC3, we used Affymetrix DNA microarrays to compare the expressions of 22.000 genes in vitro and in the corresponding xenografts. We identified 228 genes overexpressed in xenografts and characterized the implication of one of them, WSB1, in the control of apoptosis and cell proliferation. WSB1 generates 3 alternatively spliced transcripts encoding distinct protein isoforms. In xenografts and in human pancreatic tumors, global expression of WSB1 mRNA is modestly increased whereas isoform 3 is strongly overexpressed and isoforms 1 and 2 are down-regulated. Treating Mia-PaCa2 cells with stress-inducing agents induced similar changes. Whereas retrovirus-forced expression of WSB1 isoforms 1 and 2 promoted cell growth and sensitized the cells to gemcitabine- and doxorubicin-induced apoptosis, WSB1 isoform 3 expression reduced cell proliferation and enhanced resistance to apoptosis, showing that stress-induced modulation of WSB1 alternative splicing increases resistance to apoptosis of pancreatic cancer cells. CONCLUSIONS/SIGNIFICANCE: Data on WSB1 regulation support the hypothesis that activation of stress-response mechanisms helps cancer cells establishing metastases and suggest relevance to cancer development of other genes overexpressed in xenografts.

  8. Role of fibrillar Tenascin-C in metastatic pancreatic cancer.

    Science.gov (United States)

    Chen, Jian; Chen, Zhiyu; Chen, Ming; Li, Dajiang; Li, Zhihua; Xiong, Yan; Dong, Jiahong; Li, Xiaowu

    2009-04-01

    Interaction of cancer cells with stroma cells facilitates tumor progression by rebuilding the existing extracellular matrix (ECM) microenvironment. In the tumor, upregulation of Tenascin-C (Tn-C) expression potentially can alter tumor behavior. However, the molecular mechanisms by which tumor-stroma interactions affect the tumor microenvironment have not been well characterized. In this study, we analyzed the expression of fibrillar Tn-C (fTn-C) in human metastatic pancreatic cancers. After co-culturing two pancreatic cancer cell lines, highly metastatic BxPc3 cells and non-metastatic PaCa2 cells, with stromal fibroblasts (SF), we evaluated the roles of matrix metalloproteinase 2 (MMP-2) activation and SF in promoting Tn-C organization. Next, we evaluated whether fibrillar Tn-C promotes pancreatic cancer cell movement using cell adhesion and migration assays. Finally, we observed the relationship between MMP-2 activation and fTn-C formation in vivo by injecting the BxPc3 and PaCa2 cells into nude mice. We found that fTn-C was increased in metastatic pancreatic cancer. The fTn-C expression correlated with MMP-2 activity. In the in vitro co-culture, fTn-C organization was found only in BxPc3/SF co-cultures, and required the participation of active MMP-2. The fTn-C reduced cell adhesion and promote pancreatic cancer cell migration by decreasing the adhesive interactions between integrin alpha6beta1 and the ECM. The in vivo tumorigenesis analysis showed that the fTn-C formation and active MMP-2 were significantly increased in the BxPc3 tumors, compared to the PaCa2 tumors. These results demonstrate that Tn-C deposition into the ECM requires participation of active MMP-2 and SF. The deposited Tn-C could promote pancreatic cancer progression.

  9. Notch pathway activation is associated with pancreatic cancer treatment failure.

    Science.gov (United States)

    Lee, Jin Young; Song, Si Young; Park, Jeong Youp

    2014-01-01

    Pancreatic cancer is resistant to conventional treatment. The aim of the study was to confirm the hypothesis that changes in cancer stem cells (CSCs) and developmental pathway after treatment was responsible for treatment failure in pancreatic cancer. After recovery from a gemcitabine treatment, the percentage of pancreatic cancer CSCs and Notch pathway in BxPC3 and HPAC pancreatic cancer cell lines were analyzed by FACS (CD24 and CD44) and western blot (Notch1, Hes1, β-catenin, and pAKT). The effect of DAPT, a gamma-secretase inhibitor, was similarly investigated. The association between immunohistochemical expression of Hes1 and survival was analyzed. The percentage of CD24(+)CD44(+) cells was higher in gemcitabine-treated BxPC3 and HPAC cells than at pre-treatment. CD24(+)CD44(+) cells sorted from the gemcitabine-treated cell lines showed higher migration and invasion ability than CD24(-)CD44(-) or CD24(-)CD44(+) cells from the same cell lines. Western blot analysis showed an increased expression of Notch1 and Hes1 in gemcitabine-treated cell lines. The overall survival of pancreatic cancer patients with strong expression of Hes1 was shorter than that in patients with no or weak expression (11.1 vs. 21.6 months, P = 0.036). Treatment with DAPT reversed the increase in Hes1, β-catenin, and pAKT expression and the proportion of CD24(+)CD44(+) cells in gemcitabine-treated cell lines. The treatment also decreased migration and invasion ability. Our data suggested that an increase in CSCs and activation of the Notch pathway might contribute to the failure of treatment in pancreatic cancer. Notch pathway can be a potential target to overcome treatment failure. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  10. Host sphingosine kinase 1 worsens pancreatic cancer peritoneal carcinomatosis.

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Katsuta, Eriko; Ramanathan, Rajesh; Idowu, Michael O; Spiegel, Sarah; Takabe, Kazuaki

    2016-10-01

    There are no effective treatments for pancreatic cancer peritoneal carcinomatosis (PC) or cancer dissemination in abdominal cavity. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays critical roles in cancer progression. We reported that SphK1, but not SphK2, is responsible for S1P export from breast cancer cells and recently discovered that S1P is linked to inflammation and cancer in colitis-associated cancer progression. Given the fact that inflammation is known to be essential for the establishment and progression of PC, we hypothesized that SphK1 in the host animals is involved in progression of pancreatic cancer PC. Murine pancreatic adenocarcinoma panc02-luc cells were intraperitoneally injected into wildtype or SphK1 knockout (KO) mice to generate a syngeneic PC model. Cell proliferation and apoptosis were determined by Ki67 and TUNEL staining, respectively. All the animals developed panc02-luc PC. SphK1 KO mice developed significantly less tumor burden, less total tumor weight, and fewer number of PC nodules at 14 d after implantation. Histologically, less inflammatory cell infiltration and less cancer cell proliferation were observed in the tumors. There was no difference in apoptosis. Our results raise an intriguing possibility that S1P generated by SphK1 in the host promotes pancreatic cancer PC progression by stimulation of proliferation of cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Molecular mechanism of bitter melon juice efficacy against pancreatic cancer. | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Pancreatic cancer (PanC) is an aggressive disease;median life of PanC patients post-diagnosis is been tested in several clinical trials for its anti-diabetic effects and has plenty of human safety data. We, therefore, anticipate that the positive outcomes from the proposed studies will provide compelling rationale for initiating clinical trials to establish BMJ activity against human pancreatic cancer. |

  12. File list: Unc.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

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  16. File list: Oth.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

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  17. Decision making in the treatment of pancreatic cancer : a retrospective analysis

    NARCIS (Netherlands)

    J.H.G. Klinkenbijl (Jean)

    1994-01-01

    textabstractPancreatic cancer is a major and often frustrating disease in clinical gastroenterology. Diagnosis and treatment are very difficult; 90% of all patients diagnosed with pancreatic cancer die within one year after diagnosis has been made. The incidence of pancreatic cancer has increased st

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  1. Study on the biological characteristics of pancreatic cancer vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    李雷

    2012-01-01

    Objective To explore the biological characteristics of pancreatic cancer vascular endothelial cells,including the aspects of morphology,species,genetics,vascular formation ability,and proliferation ability in vitro. Methods The human pancreatic cancer cells were inoculated in nude mice pancreas to get pancreatic cancer

  2. File list: ALL.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

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  3. File list: Pol.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Unc.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

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  5. File list: ALL.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

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  6. File list: His.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Oth.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC).

    Science.gov (United States)

    Zdenkowski, Nicholas; Radvan, George; Pugliese, Leanna; Charlton, Julie; Oldmeadow, Christopher; Fraser, Allison; Bonaventura, Antonino

    2017-06-01

    Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer. Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA). Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1-48.7) weeks in the control group, and 67.6 (95% CI 14.1-98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted. Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.

  9. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  10. MicroRNA biomarkers in whole blood for detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Dehlendorff, Christian; Jensen, Benny V

    2014-01-01

    IMPORTANCE: Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES: To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels...... of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS: A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC...... (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer...

  11. Obesity, autophagy and the pathogenesis of liver and pancreatic cancers.

    Science.gov (United States)

    Aghajan, Mariam; Li, Ning; Karin, Michael

    2012-03-01

    Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor-κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  12. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  13. The Smad family and its role in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    P Singh

    2011-01-01

    Full Text Available One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  14. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samm, Nicole; Werner, Kristin; Rückert, Felix; Saeger, Hans Detlev; Grützmann, Robert; Pilarsky, Christian, E-mail: christian.pilarsky@uniklinikum-dresden.de [Department of Visceral-, Thoracic-and Vascular-Surgery, University Hospital Dresden, Dresden (Germany)

    2010-12-23

    Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-x{sub L} and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

  15. Use of incretin agents and risk of pancreatic cancer

    DEFF Research Database (Denmark)

    Knapen, L M; van Dalem, J; Keulemans, Y C;

    2016-01-01

    of pancreatic cancer in those recently initiating incretin agents is likely to be caused by protopathic bias or other types of unknown distortion. The presence of considerable confounding by disease severity and the lack of a duration-of-use relationship do not support a causal explanation for the association......AIM: To investigate the association between the use of incretin agents and the risk of pancreatic cancer. METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink, 2007-2012, was conducted. Patients (n = 182 428) with at least one non......-insulin antidiabetic drug (NIAD) prescription and aged ≥18 years during data collection, were matched one-to-one to control patients without diabetes. Multivariable Cox proportional hazards models and a new user design were used to estimate the hazard ratio (HR) of pancreatic cancer in incretin users (n = 28 370...

  16. State of the art biological therapies in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most lethal malignancies with a five-year survivalrate of approximately 5%. Several target agents havebeen tested in PDAC, but almost all have failed todemonstrate efficacy in late phase clinical trials, despitethe better understanding of PDAC molecular biologygenerated by large cancer sequencing initiatives in thepast decade. Eroltinib (a small-molecule tyrosine-kinaseinhibitor of epidermal growth factor receptor) plusgemcitabine is the only schedule with a biological agentapproved for advanced pancreatic cancer, but it hasresulted in a very modest survival benefit in unselectedpatients. In our work, we report a summary of the mainclinical trials (closed and ongoing) that refer to biologicaltherapy evaluation in pancreatic cancer treatment.

  17. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    Science.gov (United States)

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  18. The Impact of Obesity on Gallstone Disease, Acute Pancreatitis, and Pancreatic Cancer.

    Science.gov (United States)

    Cruz-Monserrate, Zobeida; Conwell, Darwin L; Krishna, Somashekar G

    2016-12-01

    Obesity is a well-recognized risk factor for gallstone formation and increases the risk for gallstone-related complications. Pancreatic diseases are impacted adversely by obesity. Although weight loss surgery increases the risk of gallstone disease, evidence suggests that bariatric surgery mitigates the obesity-associated adverse prognostication in acute pancreatitis. Obesity is also a significant risk factor for pancreatic cancer. Obesity is a global epidemic and is increasing worldwide and among all age groups. There is an urgent need for focused health policies aimed at reducing the incidence and prevalence of obesity. This article summarizes the current literature highlighting the association between obesity and the pathophysiology and outcome of gallstone disease, pancreatitis, and pancreatic cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Expression profiling identifies microRNA signature in pancreatic cancer

    OpenAIRE

    Lee, Eun Joo; Gusev, Yuriy; Jiang, Jinmai; Gerard J Nuovo; Lerner, Megan R; Frankel, Wendy L.; Morgan, Daniel L.; Postier, Russell G.; Brackett, Daniel J; Schmittgen, Thomas D.

    2007-01-01

    microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pan...

  20. Pirfenidone inhibits pancreatic cancer desmoplasia by regulating stellate cells.

    Science.gov (United States)

    Kozono, Shingo; Ohuchida, Kenoki; Eguchi, Daiki; Ikenaga, Naoki; Fujiwara, Kenji; Cui, Lin; Mizumoto, Kazuhiro; Tanaka, Masao

    2013-04-01

    Pancreatic stellate cells (PSC), which are implicated in desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress desmoplasia and exert antitumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCC), supernatants of pirfenidone-treated PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of PSCs and the deposition of collagen type I and periostin in tumors. In mice with orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating PSCs.

  1. Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis

    Science.gov (United States)

    Lu, Pei-Ying; Shu, Long; Shen, Shan-Shan; Chen, Xu-Jiao; Zhang, Xiao-Yan

    2017-01-01

    A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77–0.95; p = 0.004) and light–moderate drinking patterns (OR = 0.90; 95% CI: 0.83–0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06–1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10–1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light–moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings. PMID:28067765

  2. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

  3. Current Status of Immunotherapy Treatments for Pancreatic Cancer.

    Science.gov (United States)

    Jimenez-Luna, Cristina; Prados, Jose; Ortiz, Raul; Melguizo, Consolacion; Torres, Carolina; Caba, Octavio

    Pancreatic cancer (PC) is a lethal disease representing the seventh most frequent cause of death from cancer worldwide. Resistance of pancreatic tumors to current treatments leads to disappointing survival rates, and more specific and effective therapies are urgently needed. In recent years, immunotherapy has been proposed as a promising approach to the treatment of PC, and encouraging results have been published by various preclinical and clinical studies. This review provides an overview of the latest developments in the immunotherapeutic treatment of PC and summarizes the most recent and important clinical trials.

  4. Using digital surveillance to examine the impact of public figure pancreatic cancer announcements on media and search query outcomes.

    Science.gov (United States)

    Noar, Seth M; Ribisl, Kurt M; Althouse, Benjamin M; Willoughby, Jessica Fitts; Ayers, John W

    2013-12-01

    Announcements of cancer diagnoses from public figures may stimulate cancer information seeking and media coverage about cancer. This study used digital surveillance to quantify the effects of pancreatic cancer public figure announcements on online cancer information seeking and cancer media coverage. We compiled a list of public figures (N = 25) who had been diagnosed with or had died from pancreatic cancer between 2006 and 2011. We specified interrupted time series models using data from Google Trends to examine search query shifts for pancreatic cancer and other cancers. Weekly media coverage archived on Google News were also analyzed. Most public figures' pancreatic cancer announcements corresponded with no appreciable change in pancreatic cancer search queries or media coverage. In contrast, Patrick Swayze's diagnosis was associated with a 285% (95% confidence interval [CI]: 212 to 360) increase in pancreatic cancer search queries, though it was only weakly associated with increases in pancreatic cancer media coverage. Steve Jobs's death was associated with a 197% (95% CI: 131 to 266) increase in pancreatic cancer queries and a 3517% (95% CI: 2882 to 4492) increase in pancreatic cancer media coverage. In general, a doubling in pancreatic cancer-specific media coverage corresponded with a 325% increase in pancreatic cancer queries. Digital surveillance is an important tool for future cancer control research and practice. The current application of these methods suggested that pancreatic cancer announcements (diagnosis or death) by particular public figures stimulated media coverage of and online information seeking for pancreatic cancer.

  5. Vitamin D for the prevention and treatment of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Kun-Chun Chiang; Tai C Chen

    2009-01-01

    Pancreatic cancer is ranked fifth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy,leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identified during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells invivoand in vitro, including breast, prostate, and colon.Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore,1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a preclinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol),is effective in inhibiting tumor growth invitroand invivo, viaupregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.(c) 2009 The WJG Press and Baishideng. All rights reserved.

  6. Strategy to differentiate autoimmune pancreatitis from pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Kensuke Takuma; Terumi Kamisawa; Rajesh Gopalakrishna; Seiichi Hara; Taku Tabata; Yoshihiko Inaba; Naoto Egawa

    2012-01-01

    Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms.Based on histological and immunohistochemical examinations of various organs of AIP patients,AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease".Clinically,AIP patients and patients with pancreatic cancer share many features,such as preponderance of elderly males,frequent initial symptom of painless jaundice,development of new-onset diabetes mellitus,and elevated levels of serum tumor markers.It is of uppermost importance not to misdiagnose AIP as pancreatic cancer.Since there is currently no diagnostic serological marker for AIP,and approach to the pancreas for histological examination is generally difficult,AIP is diagnosed using a combination of clinical,serological,morphological,and histopathological features.Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography,presence of other organ involvement such as bilateral salivary gland swelling,retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis;negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness.Since AIP responds dramatically to steroid therapy,accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

  7. Functional annotation of rare gene aberration drivers of pancreatic cancer | Office of Cancer Genomics

    Science.gov (United States)

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC).

  8. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Directory of Open Access Journals (Sweden)

    Juan L. Iovanna

    2010-12-01

    Full Text Available Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  9. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie, E-mail: sophie.vasseur@inserm.fr; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  10. Current Challenges and Opportunities for Chemoprevention of Pancreatic Cancer.

    Science.gov (United States)

    Mohammed, Altaf; Janakiram, Naveena B; Madka, Venkateshwar; Li, Min; Asch, Adam S; Rao, Chinthalapally V

    2017-02-08

    The incidence of pancreatic cancer (PC) is rising in parallel with the deaths caused by this malignant disease largely due to limited improvement in current treatment strategies. In spite of aggressive PC research, for the past three decades, there has been no significant improvement in the five-year survival for this cancer. Like many other cancers, it takes several years for normal pancreatic cells to transform into pancreatic precursor lesions and to further progress into invasive carcinoma. Hence there is a scope for development of chemoprevention strategies to inhibit/delay/prevent progression of this disease into an advanced stage cancer. Availability of various genetically engineered mouse (GEM) models of PC has led to accelerated progress in understanding the disease and developing intervention strategies otherwise stalled for a long time. These GEM models spontaneously develop PC in a stepwise manner and mimic the disease etiology in humans. Understanding PC development from initiation to progression to metastasis is very important for early detection and prevention of PC. In this review, we focus on the current situation, the potential challenges, the progress in existing strategies and available opportunities as well as suggest key areas for research within the increasingly important area of pancreatic cancer chemoprevention.

  11. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Zamora-Ros, Raul; Bueno-de-Mesquita, H. Bas; Wark, Petra A.; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C.; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Quirós, José Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H.; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie Christine; Clavel-Chapelon, Françoise; Cross, Amanda J.; Lu, Yunxia; Riboli, Elio; Duell, Eric J.

    2016-01-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the E

  12. Dynamic contrast-enhanced CT in patients with pancreatic cancer

    DEFF Research Database (Denmark)

    Lauridsen, Carsten Ammitzbøl; Eriksen, Rie Østbjerg; Strauch, Louise Søborg;

    2016-01-01

    tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful......The aim of this systematic review is to provide an overview of the use of Dynamic contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library...... in the investigation of characteristic vascular patterns of pancreatic exocrine tumors. Further clinical studies are desired for investigating the potential of DCE-CT in pancreatic tumors. Keywords:...

  13. Pharmacological reversal of histone methylation presensitizes pancreatic cancer cells to nucleoside drugs: in vitro optimization and novel nanoparticle delivery studies

    National Research Council Canada - National Science Library

    Hung, Sau Wai; Mody, Hardik; Marrache, Sean; Bhutia, Yangzom D; Davis, Franklin; Cho, Jong Hyun; Zastre, Jason; Dhar, Shanta; Chu, Chung K; Govindarajan, Rajgopal

    2013-01-01

    ...), in improving the chemosensitivity of pancreatic cancer to nucleoside analogs (i.e., gemcitabine). DZNep brought delayed but selective cytotoxicity to pancreatic cancer cells without affecting normal human pancreatic ductal epithelial...

  14. Dietary mutagen exposure and risk of pancreatic cancer.

    Science.gov (United States)

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  15. Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers.

    Science.gov (United States)

    Bronte, Vincenzo; Tortora, Giampaolo

    2016-08-01

    Obesity-induced inflammation can build up a confined microenvironment in pancreatic adenocarcinoma that is associated with increased desmoplasia, neutrophil recruitment, reduced delivery of chemotherapeutic drugs, and immune evasion. Targeting molecular pathways empowering this circuit might represent a necessary measure to reach clinical efficacy for combination therapies in patients with excess body weight. Cancer Discov; 6(8); 821-3. ©2016 AACR.See related article by Incio et al., p. 852. ©2016 American Association for Cancer Research.

  16. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies.

    Science.gov (United States)

    Chiorean, Elena Gabriela; Coveler, Andrew L

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%-90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of "precision therapeutics". No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease.

  17. Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

    Science.gov (United States)

    Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

    2013-06-01

    Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

  18. Pancreatic cancer: Translational research aspects and clinical implications

    Institute of Scientific and Technical Information of China (English)

    Daniel Ansari; Bi-Cheng Chen; Lei Dong; Meng-Tao Zhou; Roland Andersson

    2012-01-01

    Despite improvements in surgical techniques and adjuvant chemotherapy,the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%.This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes,proteins,microRNAs or epigenetic modifications.However,there are still major hurdles when translating investigational biomarkers into routine clinical practice.Furthermore,novel ways of secondary screening in high-risk individuals,such as artificial neural networks and modern imaging,will be discussed.Drug resistance is ubiquitous in pancreatic cancer.Several mechanisms of drug resistance have already been revealed,including human equilibrative nucleoside transporter-1 status,multidrug resistance proteins,aberrant signaling pathways,microRNAs,stromal influence,epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells.These factors must be considered when developing more customized types of intervention ("personalized medicine").In the future,multifunctional nanoparticles that combine a specific targeting agent,an imaging probe,a cell-penetrating agent,a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer.

  19. Metformin and pancreatic cancer: Is there a role?

    Science.gov (United States)

    De Souza, Andre; Khawaja, Khadija Irfan; Masud, Faisal; Saif, Muhammad Wasif

    2016-02-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA, with a 5-year survival rate of 6 %. Anti-hyperglycemic treatments for type 2 diabetes mellitus that induce hyperinsulinemia (i.e., sulfonylureas) are thought to increase cancer risk, whereas treatments that lower insulin resistance and hyperinsulinemia (i.e., metformin) are considered cancer prevention strategies. Metformin is a cornerstone in the treatment of diabetes mellitus type 2. Retrospective studies have shown a survival benefit in diabetic patients with many solid tumors including pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Ongoing research is redefining our understanding about how metformin modulates the molecular pathways implicated in pancreatic cancer. The authors review the topic critically and also give their opinion. Further studies investigating the effect of metformin in combination with chemotherapy, targeted agents, or radiation therapy are undergoing. In addition, the role of metabolic and other biomarkers is needed.

  20. Prognostic value of metastin expression in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Kawaguchi Yoshiya

    2009-01-01

    Full Text Available Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay. Results Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%, while strong expression of GPR54 was detected in 30 tumors (56.6%. Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047. Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04. Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02. Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03, and the patients with a high plasma metastin level (n = 6 did not die after surgical resection. Conclusion Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.

  1. The Geography of Cancer Mortality in Japan Focusing on Pancreatic Malignancies

    OpenAIRE

    YAMAGUCHI, Natsu; Tanabe, Tsuyoshi; Oshiro, Hitoshi; Nakabayashi, Narue; Amano, Hiroki; Fujita, Yasuyuki

    2011-01-01

    To identify pancreatic cancer’s etiology and to better understand its pathogenesis, we assessed the association between pancreatic and other cancers by determining the standardized mortality ratios (SMRs). We calculated sex-specific and partial correlations (adjusting for lung cancer SMR) between pancreatic and other cancers in 47 Japanese prefectures. Comparing the results for the decades 1998-2007, 1988-1997, and 1978-1987 revealed that pancreatic cancer’s SMR associates with those of lung,...

  2. Association between Alcohol Consumption, Folate Intake, and Risk of Pancreatic Cancer: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Winta Yellow

    2017-05-01

    Full Text Available Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3% of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls in a largely white population (>96%. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day. Our study showed dietary folate intake had a modest effect size, but was significantly inversely associated with pancreatic cancer (odds ratio (OR = 0.99, p < 0.0001. The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

  3. Myxoma Virus Sensitizes Cancer Cells to Gemcitabine and Is an Effective Oncolytic Virotherapeutic in Models of Disseminated Pancreatic Cancer

    OpenAIRE

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M.; Mona, Mahmoud; McFadden, Grant

    2012-01-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and comb...

  4. GEMMs as preclinical models for testing pancreatic cancer therapies

    Directory of Open Access Journals (Sweden)

    Aarthi Gopinathan

    2015-10-01

    Full Text Available Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs, the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL-KrasG12D; LSL-Trp53R172H; Pdx1-cre (KPC model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.

  5. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice.

    Directory of Open Access Journals (Sweden)

    Meredith A Collins

    Full Text Available Pancreatic cancer is one of the deadliest human malignancies, and its prognosis has not improved over the past 40 years. Mouse models that spontaneously develop pancreatic adenocarcinoma and mimic the progression of the human disease are emerging as a new tool to investigate the basic biology of this disease and identify potential therapeutic targets. Here, we describe a new model of metastatic pancreatic adenocarcinoma based on pancreas-specific, inducible and reversible expression of an oncogenic form of Kras, together with pancreas-specific expression of a mutant form of the tumor suppressor p53. Using high-resolution magnetic resonance imaging to follow individual animals in longitudinal studies, we show that both primary and metastatic lesions depend on continuous Kras activity for their maintenance. However, re-activation of Kras* following prolonged inactivation leads to rapid tumor relapse, raising the concern that Kras*-resistance might eventually be acquired. Thus, our data identifies Kras* as a key oncogene in pancreatic cancer maintenance, but raises the possibility of acquired resistance should Kras inhibitors become available for use in pancreatic cancer.

  6. Current Surgical Aspects of Palliative Treatment for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Karapanos, Konstantinos, E-mail: dr.kostaskarapanos@gmail.com; Nomikos, Iakovos N. [Department of Surgery (B' Unit), METAXA Cancer Memorial Hospital, Piraeus (Greece)

    2011-02-11

    Despite all improvements in both surgical and other conservative therapies, pancreatic cancer is steadily associated with a poor overall prognosis and remains a major cause of cancer mortality. Radical surgical resection has been established as the best chance these patients have for long-term survival. However, in most cases the disease has reached an incurable state at the time of diagnosis, mainly due to the silent clinical course at its early stages. The role of palliative surgery in locally advanced pancreatic cancer mainly involves patients who are found unresectable during open surgical exploration and consists of combined biliary and duodenal bypass procedures. Chemical splanchnicectomy is another modality that should also be applied intraoperatively with good results. There are no randomized controlled trials evaluating the outcomes of palliative pancreatic resection. Nevertheless, data from retrospective reports suggest that this practice, compared with bypass procedures, may lead to improved survival without increasing perioperative morbidity and mortality. All efforts at developing a more effective treatment for unresectable pancreatic cancer have been directed towards neoadjuvant and targeted therapies. The scenario of downstaging tumors in anticipation of a future oncological surgical resection has been advocated by trials combining gemcitabine with radiation therapy or with the tyrosine kinase inhibitor erlotinib, with promising early results.

  7. Early precursors of pancreatic cancer in college men.

    Science.gov (United States)

    Whittemore, A S; Paffenbarger, R S; Anderson, K; Halpern, J

    1983-01-01

    From college data on 50,000 male former students, the records of 126 men who died of pancreatic cancer in a 16-50 yr follow-up period were compared with those of 504 surviving classmates with respect to physical and social characteristics. Return mail questionnaires received from 30,000 surviving alumni in 1962 or 1966 also were reviewed for characteristics that might predict altered risk of pancreatic cancer. Strong positive associations were found for cigarette smoking as reported both during college (p less than 0.001) and at time of questionnaire return (p = 0.03). Smoking 10 or more cigarettes per day during college corresponded to a relative risk of 2.6 with 95% confidence limits 1.5 to 4.6, and a positive smoking history at questionnaire return yielded a relative risk of 2.4 (1.1-5.1). No association was found for collegiate coffee drinking, either before or after adjustment for cigarette smoking. The relative risk for coffee drinking adjusted for smoking was 1.1 (0.7-1.8). In contrast, collegiate tea consumption was associated with a reduction in pancreatic cancer risk. The relative risk for tea drinking adjusted for smoking was 0.5 (0.3-0.9). Men who at college physical examination complained of occasional abdominal pain or discomfort had increased relative risk of pancreatic cancer (3.1 : 1.1-9.0) in the follow-up period.

  8. Knowledge discovery for pancreatic cancer using inductive logic programming.

    Science.gov (United States)

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

  9. Obesity potentiates the growth and dissemination of pancreatic cancer.

    Science.gov (United States)

    Zyromski, Nicholas J; Mathur, Abhishek; Pitt, Henry A; Wade, Terrence E; Wang, Sue; Nakshatri, Poornima; Swartz-Basile, Deborah A; Nakshatri, Harikrishna

    2009-08-01

    Obesity is an independent risk factor for pancreatic cancer development and progression, although the mechanisms underlying this association are completely unknown. The aim of the current study was to investigate the influence of obesity on pancreatic cancer growth using a novel in vivo model. Lean (C57BL/6 J) and obese (Lep(Db) and Lep(Ob)) mice were inoculated with murine pancreatic cancer cells (PAN02), and studied after 5 weeks of tumor growth. Tumor histology was evaluated by hematoxylin and eosin staining, cellular proliferation was assessed by 5-bromodeoxyuridine, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Serum adiponectin, leptin, and insulin levels were assayed. Obese mice developed larger tumors, and a significantly greater number of mice developed metastases; mortality was also greater in obese mice. Tumor apoptosis did not differ among strains, but tumors from both obese strains had greater proliferation relative to those growing in lean animals. Serum adiponectin concentration correlated negatively and serum insulin concentration correlated positively with tumor proliferation. Intratumoral adipocyte mass in tumors from both obese strains was significantly greater than that in tumors of lean mice. Data from this novel in vivo model suggest that the altered adipokine milieu and insulin resistance observed in obesity may lead directly to changes in tumor microenvironment, thereby promoting pancreatic cancer growth and dissemination.

  10. Evaluation and treatment of stage IVb pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Hidenori; Kurita, Nobuhiro; Miyake, Hidenori [Tokushima Univ. (Japan). School of Medicine] [and others

    2003-04-01

    Pancreatic cancer is often detected in a far advanced stage and the prognosis is still extremely poor. A clinicopathological study was made on 49 patients with Stage IVb pancreatic cancer treated at our department from March 1994 to February 2002. In this study, patient factors (age and gender), tumor factors (hepatic metastasis, peritoneal dissemination, and distant metastasis), and treatment factors (systemic chemotherapy, intra- and post-operative radiotherapy, some treatments to hepatic metastasis, and surgical resection) were examined, and the survival was evaluated statistically. Overall mean survival was 150 days and the 1-year survival rate was 0%. With multivariate analysis, prognostic factors were hepatic metastasis, peritoneal dissemination and some treatments to hepatic metastasis. In advanced pancreatic cancer with hepatic metastasis, the prognostic factor was just some treatments to hepatic metastasis. Systemic chemotherapy with somatostatin analog was ineffective. At present we use either gemcitabine or 5FU in systemic chemotherapy for Stage IVb pancreatic cancers without hepatic metastasis, and conduct hepatic arterial infusion therapy for those with hepatic metastasis. (author)

  11. Pancreatic cancer: Incidence, clinical profile, and frequency of ...

    African Journals Online (AJOL)

    Hana T. Al-Majed

    2012-08-09

    Aug 9, 2012 ... Methods: The study design was a retrospective hospital-based record study in which records of 251 ... Peer review under the responsibility of Alexandria University Faculty ... adenomas, cysts, or unknown primary tumors; concurrent ..... onset of pancreatic cancer: evidence of a major role for smoking.

  12. Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Alireza Tavassoli

    2013-08-01

    Full Text Available Introduction : Severepain is a major problem in patients with unresectable pancreatic cancer. The goal of this study is to evaluate the effects of Thoracoscopic Splanchnicectomy (TS on pain control in these patients suffering from unresectable pancreatic cancer. Methods:Between years 2000 to 2011, 20 patients suffering from unresectable pancreatic cancer underwent TS due to severe pain. They were studied in terms of age, sex, location of pancreas tumor, history of previous surgery, response to treatments for pain control (assessed with VAS scoring system and complications of surgery. Results:M/F = 14/6 with a mean age of 63 years. The most common tumour site was at the pancreas head (in 8 patients. The most cause of unresectability was local expansion to critical adjacent elements (in 10 patients. Surgery was performed successfully in all patients. Post-operative complication included only pleural effusion on the left side which was cured by proper treatment. There were no post-op mortalities.  15 patients had acceptable levels of pain at the end of a six month follow-up period. ConclusionTS provides good pain control, little side effects and minimal invasiveness, the technique is recommended for pain control in patients with unresectable pancreatic cancer.

  13. The genetics of nicotine dependence: Relationship to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Stewart L MacLeod; Parimal Chowdhury

    2006-01-01

    Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer.Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence,addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. Tn addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However,there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

  14. Routine testing for PALB2 mutations in familial pancreatic cancer families and breast cancer families with pancreatic cancer is not indicated

    NARCIS (Netherlands)

    Harinck, Femme; Kluijt, Irma; van Mil, Saskia E.; Waisfisz, Quinten; van Os, Theo A. M.; Aalfs, Cora M.; Wagner, Anja; Olderode-Berends, Maran; Sijmons, Rolf H.; Kuipers, Ernst J.; Poley, Jan-Werner; Fockens, Paul; Bruno, Marco J.

    2012-01-01

    PALB2-mutation carriers not only have an increased risk for breast cancer (BC) but also for pancreatic cancer (PC). Thus far, PALB2 mutations have been mainly found in PC patients from families affected by both PC and BC. As it is well known that the prevalence of gene mutations varies between diffe

  15. CLINICAL USE OF COMBINED DETECTION WITH TUMOR MARKERS FOR PANCREATIC CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To explore the value of clinical use of combined detection with tumor markers for pancreatic cancer. Methods Tumor markers CA242,CA19-9 and CA50 in serum of 32 patinets with pancreatic cancer;26 patients with non-pancreatic digestive tract cancers and 24 patietns with benign pancreatic or biliary tract diseases were measured by immunoradiometric assay (IRMA). Results The levels of three markers in serum and positive rates of patients with pancreatic cancer were higher than those of other patients. The effect of measurement combining CA242 with CA19-9 was the best. The sensitivity ,specificity and accuracy of diagnosis for pancreatic cancer were 92.6%, 73.8% and 81.2% respectively. The levels of CA242 and CA19-9 were positively relative to burden of pancreatic cancer, and serum levels of these two markers of patients with resectable pancreatic cancer were lower than those with unresectable, but on difference was observed for CA50. Conclusion Combined detection of serum CA242 and CA19-9 could prove the effectual indicator for finding the patients with pancreatic cancer in high risk population or for resectable pancreatic cancer. Pre-operative measurement of serum levels of CA242 and CA19-9 is helpful to evaluate the burden of the tumors and possiblity of resect for pancreatic cancers.

  16. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ross C. Smith

    2011-04-01

    Full Text Available Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC. Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (~100 µm diameter, causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of

  17. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J., E-mail: barry.allen@sesiahs.health.nsw.gov.au; Abbas Rizvi, Syed M.; Qu, Chang F. [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah, 2217 (Australia); Smith, Ross C. [Cancer Surgery Laboratory, Northern Clinical School, University of Sydney, Kolling Institute, Royal North Shore Hospital, St. Leonards, NSW 2065 (Australia)

    2011-04-01

    Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope {sup 213}Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

  18. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  19. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    Science.gov (United States)

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  20. Imaging pancreatic cancer using bioconjugated InP quantum dots.

    Science.gov (United States)

    Yong, Ken-Tye; Ding, Hong; Roy, Indrajit; Law, Wing-Cheung; Bergey, Earl J; Maitra, Anirban; Prasad, Paras N

    2009-03-24

    In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

  1. Pancreatic cancer: Are "liquid biopsies" ready for prime-time?

    Science.gov (United States)

    Lewis, Alexandra R; Valle, Juan W; McNamara, Mairead G

    2016-08-28

    Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA (ctDNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ctDNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.

  2. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Xu; Jun Hu; Min Wang; Feng Peng; Rui Tian; Xing-Jun Guo; Yu Xie; Ren-Yi Qin

    2016-01-01

    BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopula-tions are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-culturedwithnormalperipheralbloodmononuclearcells(PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se-rum of patients with pancreatic cancer. CONCLUSIONS: MDSCsweretumorrelated:tumorcellsinduced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

  3. Calmodulin antagonists promote TRA-8 therapy of resistant pancreatic cancer.

    Science.gov (United States)

    Yuan, Kaiyu; Yong, Sun; Xu, Fei; Zhou, Tong; McDonald, Jay M; Chen, Yabing

    2015-09-22

    Pancreatic cancer is highly malignant with limited therapy and a poor prognosis. TRAIL-activating therapy has been promising, however, clinical trials have shown resistance and limited responses of pancreatic cancers. We investigated the effects of calmodulin(CaM) antagonists, trifluoperazine(TFP) and tamoxifen(TMX), on TRA-8-induced apoptosis and tumorigenesis of TRA-8-resistant pancreatic cancer cells, and underlying mechanisms. TFP or TMX alone did not induce apoptosis of resistant PANC-1 cells, while they dose-dependently enhanced TRA-8-induced apoptosis. TMX treatment enhanced efficacy of TRA-8 therapy on tumorigenesis in vivo. Analysis of TRA-8-induced death-inducing-signaling-complex (DISC) identified recruitment of survival signals, CaM/Src, into DR5-associated DISC, which was inhibited by TMX/TFP. In contrast, TMX/TFP increased TRA-8-induced DISC recruitment/activation of caspase-8. Consistently, caspase-8 inhibition blocked the effects of TFP/TMX on TRA-8-induced apoptosis. Moreover, TFP/TMX induced DR5 expression. With a series of deletion/point mutants, we identified CaM antagonist-responsive region in the putative Sp1-binding domain between -295 to -300 base pairs of DR5 gene. Altogether, we have demonstrated that CaM antagonists enhance TRA-8-induced apoptosis of TRA-8-resistant pancreatic cancer cells by increasing DR5 expression and enhancing recruitment of apoptotic signal while decreasing survival signals in DR5-associated DISC. Our studies support the use of these readily available CaM antagonists combined with TRAIL-activating agents for pancreatic cancer therapy.

  4. Novel curcumin-loaded magnetic nanoparticles for pancreatic cancer treatment.

    Science.gov (United States)

    Yallapu, Murali M; Ebeling, Mara C; Khan, Sheema; Sundram, Vasudha; Chauhan, Neeraj; Gupta, Brij K; Puumala, Susan E; Jaggi, Meena; Chauhan, Subhash C

    2013-08-01

    Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has showed potent anticancer and cancer prevention activity in a variety of cancers. However, the clinical translation of CUR has been significantly hampered due to its extensive degradation, suboptimal pharmacokinetics, and poor bioavailability. To address these clinically relevant issues, we have developed a novel CUR-loaded magnetic nanoparticle (MNP-CUR) formulation. Herein, we have evaluated the in vitro and in vivo therapeutic efficacy of this novel MNP-CUR formulation in pancreatic cancer. Human pancreatic cancer cells (HPAF-II and Panc-1) exhibited efficient internalization of the MNP-CUR formulation in a dose-dependent manner. As a result, the MNP-CUR formulation effectively inhibited growth of HPAF-II and Panc-1 cells in cell proliferation and colony formation assays. The MNP-CUR formulation suppressed pancreatic tumor growth in an HPAF-II xenograft mouse model and improved the survival of mice by delaying tumor growth. The growth-inhibitory effect of MNP-CUR formulation correlated with the suppression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-extra large (Bcl-xL), induced myeloid leukemia cell differentiation protein (Mcl-1), cell surface-associated Mucin 1 (MUC1), collagen I, and enhanced membrane β-catenin expression. MNP-CUR formulation did not show any sign of hemotoxicity and was stable after incubation with human serum proteins. In addition, the MNP-CUR formulation improved serum bioavailability of CUR in mice up to 2.5-fold as compared with free CUR. Biodistribution studies show that a significant amount of MNP-CUR formulation was able to reach the pancreatic xenograft tumor(s), which suggests its clinical translational potential. In conclusion, this study suggests that our novel MNP-CUR formulation can be valuable for the treatment of pancreatic cancer.

  5. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...

  6. Recent advances in the surgical treatment of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    A Shankar; RCG Russell

    2001-01-01

    @@ INTRODUCTION Pancreatic cancer remains the fourth commonest cause of cancer related death in the western world[1]. The prognosis remains dismal due partly to late presentation, with associated low resectability rates, and the aggressive biological nature of these tumors. The median survival time from diagnosis in unresectable tumors remains only 4 6 months.For those patients amenable to surgical resection over the last 20 years have seen marked improvements in postoperative mortality and morbidity, especially in specialist pancreatic centres 23. Despite these changes long-term survival remains low. with a total 5-year survival rate remaining less than 5%.Patients with ampullary cancer have a better 5-year survival of 40°%-60°%.

  7. Is screening for pancreatic cancer in high-risk groups cost-effective?

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Gerdes, Anne-Marie; Sørensen, Jan;

    2016-01-01

    OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems...... with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no...

  8. Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

    Science.gov (United States)

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

    Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

  9. Preoperative assessment and optimization in periampullary and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    S Myatra

    2011-01-01

    Full Text Available Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign, stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.

  10. Pharmacogenomics and Pancreatic Cancer Treatment. Optimizing Current Therapy and Individualizing Future Therapy

    Directory of Open Access Journals (Sweden)

    Soonmo Peter Kang

    2008-05-01

    Full Text Available Each year, more than 30,000 Americans are diagnosed with pancreatic cancer. We have only made incremental advancements in treatment of pancreatic cancer despite our best efforts. Research has revealed that pancreatic cancer is a genetic disease which is associated with various forms of cancer associated genetic alterations. Identification and understanding of these carcinogenic gene alterations is the base upon which we can overcome drug resistance and develop novel treatment approaches. In this paper, we review current understanding of pharmacogenomics of pancreatic cancer treatment and address future direction of the field.

  11. ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2013-05-07

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Duct Cell Adenocarcinoma of the Pancreas; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Gallbladder Cancer; Recurrent Pancreatic Cancer; Stage II Gallbladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Pancreatic Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer

  12. Dickkopf3 overexpression inhibits pancreatic cancer cell growth in vitro

    Institute of Scientific and Technical Information of China (English)

    Yu-Mei Gu; Yi-Hui Ma; Wu-Gan Zhao; Jie Chen

    2011-01-01

    AIM: To elucidate the role of dickkopf3 (Dkk3) in human pancreatic cancer cell growth.METHODS: Dkk3 mRNA and protein expression in human pancreatic cancer cell lines were detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blotting and immunofluorescence. Methylation of the Dkk3 promoter sequence was examined by methylation-specific polymerase chain reaction (MSP) and Dkk3 mRNA expression was determined by real-time RT-PCR after 5-aza-2'-deoxycytidine (5-aza-dC) treatment. The effects of Dkk3 on cancer cell proliferation and in vitro sensitivity to gemcitabine were investigated by CellTiter 96. AQueous One Solution Cell Proliferation Assay (MTS) after transfecting the Dkk3 expression plasmid into human pancreatic cancer cells. The expression of β-catenin, phosphorylated extracellular signal-regulated protein kinases (pERK) and extracellular signal-regulated protein kinases (ERK) was also examined by real-time RT-PCR and Western blotting after upregulating Dkk3 expression in human pancreatic cancer cells.RESULTS: The results show that the expression levels of both Dkk3 mRNA and protein were low in all pancreatic cancer cell lines tested. The Dkk3 promoter sequence was methylated in the MIA PaCa-2 and AsPC-1 cell lines, which showed reduced Dkk3 expression. These two cell lines, which initially had a methylated Dkk3 promoter, showed increased Dkk3 mRNA expression that was dependent upon the dosage and timing of the DNA demethylating agent, 5-aza-dC, treatment (P < 0.05 or P < 0.01). When Dkk3 expression was upregulated following the transfection of a Dkk3 expression plasmid into MIA PaCa-2 cells, the ability of cells to proliferate decreased (P < 0.01), and the expression of β-catenin and pERK was downregulated (P < 0.01). Sensitivity to gemcitabine was enhanced in Dkk3 expression plasmid-transfected cells.CONCLUSION: Our findings, for the first time, implicate Dkk3 as a tumor suppressor in human pancreatic cancer

  13. Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

    Science.gov (United States)

    Rosenberger, I; Strauss, A; Dobiasch, S; Weis, C; Szanyi, S; Gil-Iceta, L; Alonso, E; González Esparza, M; Gómez-Vallejo, V; Szczupak, B; Plaza-García, S; Mirzaei, S; Israel, L L; Bianchessi, S; Scanziani, E; Lellouche, J-P; Knoll, P; Werner, J; Felix, K; Grenacher, L; Reese, T; Kreuter, J; Jiménez-González, M

    2015-09-28

    Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

  14. In vitro models of pancreatic cancer for translational oncology research

    Science.gov (United States)

    Feldmann, Georg; Rauenzahn, Sherri; Maitra, Anirban

    2009-01-01

    Background Pancreatic cancer is a disease of near uniform fatality and the overwhelming majority of patients succumb to their advanced malignancy within a few months of diagnosis. Despite considerable advances in our understanding of molecular mechanisms underlying pancreatic carcinogenesis, this knowledge has not yet been fully translated into clinically available treatment strategies that yield significant improvements in disease free or overall survival. Objective Cell line-based in vitro model systems provide powerful tools to identify potential molecular targets for therapeutic intervention as well as for initial pre-clinical evaluation of novel drug candidates. Here we provide a brief overview of recent literature on cell line-based model systems of pancreatic cancer and their application in the search for novel therapeutics against this vicious disease. Conclusion While in vitro models of pancreatic cancer are of tremendous value for genetic studies and initial functional screenings in drug discovery, they carry several imanent drawbacks and are often poor in predicting therapeutic response in humans. Therefore, in most instances they are successfully exploited to generate hypothesis and identify molecular targets for novel therapeutics, which are subsequently subject to further in-depth characterization using more advanced in vivo model systems and clinical trials. PMID:20160967

  15. Various diffusion magnetic resonance imaging techniques for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Meng-Yue Tang; Xiao-Ming Zhang; Tian-Wu Chen; Xiao-Hua Huang

    2015-01-01

    Pancreatic cancer is one of the most common malignanttumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging(MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging(DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed.

  16. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  17. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

    Science.gov (United States)

    Torres, Carolina; Linares, Ana; Alejandre, Maria José; Palomino-Morales, Rogelio J; Caba, Octavio; Prados, Jose; Aránega, Antonia; Delgado, Juan R; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M; Rojas, Ignacio; Perales, Sonia

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  18. SIRT1 inhibition in pancreatic cancer models: contrasing effects in vitro and in vivo

    NARCIS (Netherlands)

    Oon, Chern Ein; Strell, Carina; Yeong, Keng Yoon; Östman, Arne; Prakash, Jai

    2015-01-01

    Gemcitabine remains the standard treatment for pancreatic cancer, although most patients acquire resistance to the therapy. Up-regulated in pancreatic cancer, SIRT1 is involved in tumorigenesis and drug resistance. However the mechanism through which SIRT1 regulates drug sensitivity in cancer cells

  19. SIRT1 inhibition in pancreatic cancer models: contrasing effects in vitro and in vivo

    NARCIS (Netherlands)

    Oon, Chern Ein; Strell, Carina; Yeong, Keng Yoon; Östman, Arne; Prakash, Jai

    2015-01-01

    Gemcitabine remains the standard treatment for pancreatic cancer, although most patients acquire resistance to the therapy. Up-regulated in pancreatic cancer, SIRT1 is involved in tumorigenesis and drug resistance. However the mechanism through which SIRT1 regulates drug sensitivity in cancer cells

  20. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrej Udelnow

    Full Text Available BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of

  1. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  2. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  3. Risk Factors for Pancreatic Cancer in China: A Multicenter Case-Control Study

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    Zhaoxu Zheng

    2016-02-01

    Full Text Available Background: Despite having one of the highest mortality rates of all cancers, the risk factors of pancreatic cancer remain unclear. We assessed risk factors of pancreatic cancer in China. Methods: A case-control study design was conducted using data from four hospital-based cancer registries (Henan Provincial Cancer Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences. Controls were equally matched and selected from family members of non-pancreatic cancer patients in the same hospitals. Face-to-face interviews were conducted by trained staff using questionnaires. Conditional logistic regression models were used to assess odd ratios (ORs and 95% confident intervals (CIs. Results: Among 646 recruited participants, 323 were pancreatic cancer patients and 323 were controls. Multivariate logistic analysis suggested that pancreatic cancer family history (adjusted OR 1.23; 95% CI, 1.11–3.70, obesity (adjusted OR 1.77; 95% CI, 1.22–2.57, diabetes (adjusted OR 2.96; 95% CI, 1.48–5.92 and smoking (adjusted OR 1.78; 95% CI, 1.02–3.10 were risk factors for pancreatic cancer, but that drinking tea (adjusted OR 0.49; 95% CI, 0.25–0.84 was associated with reduced risk of pancreatic cancer. Conclusions: Cigarette smoking, family history, obesity, and diabetes are risk factors of pancreatic cancer, which is important information for designing early intervention and preventive strategies for pancreatic cancer and may be beneficial to pancreatic cancer control in China.

  4. Norepinephrine inhibits the migratory activity of pancreatic cancer cells.

    Science.gov (United States)

    Stock, Anna-Maria; Powe, Desmond G; Hahn, Stephan A; Troost, Gabriele; Niggemann, Bernd; Zänker, Kurt S; Entschladen, Frank

    2013-07-15

    We have shown previously that norepinephrine induces migratory activity of tumour cells from breast, colon and prostate tissue via activation of beta-2 adrenergic receptors. Consequently, this effect can be inhibited pharmacologically by clinically established beta-blockers. Tumour cell migration is a prerequisite for metastasis formation, and accordingly we and others have shown that breast cancer patients, which take beta-blockers due to hypertension, have reduced metastasis formation and increased survival probability as compared to patients without hypertension or using other anti-hypertensive medication. Unlike the aforementioned tumour cells, pancreatic cancer cells show a reduced migratory activity upon norepinephrine treatment. By means of our three-dimensional, collagen-based cell migration assay, we have investigated the signal transduction pathways involved in this phenomenon. We have found that this conflicting effect of norepinephrine on pancreatic cancer cells is due to an imbalanced activation of the two pathways that usually mediate a pro-migratory effect of norepinephrine in other tumour cell types. Firstly, the inhibitory effect results from activation of a pathway which causes a strong increase of the secondary cell signalling molecule, cAMP. In addition, activation of phospholipase C gamma and the downstream protein kinase C alpha were shown to be already activated in pancreatic cancer cells and cannot be further activated by norepinephrine. We hypothesize that this constitutive activation of the phospholipase C gamma pathway is due to a cross-talk with receptor tyrosine kinase signalling, and this might also deliver an explanation for the unusual high spontaneous migratory activity of pancreatic cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Kawaguchi Yoshiya; Masui Toshihiko; Koizumi Masayuki; Kida Atsushi; Ito Tatsuo; Katagiri Fumihiko; Doi Ryuichiro; Nagai Kazuyuki; Tomita Kenji; Oishi Shinya; Fujii Nobutaka; Uemoto Shinji

    2009-01-01

    Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcino...

  6. Tuft Cell Regulation of miRNAs in Pancreatic Cancer

    Science.gov (United States)

    2014-12-01

    scientific research publication ( PLoS One . 2015 Feb 27;10(2):e0118933), and one scientific presentation at the 2014 American Pancreatic Association...adenocarcinoma, PI: Courtney W. Houchen, April, 2015 – Mar, 2020). • Successfully published recently in journal PLoS ONE (Qu et al., PLoS One . 2015 Feb 27;10(2...pancreatic cancer. PloS one . 2013;8(9):e73940. doi: 10.1371/journal.pone.0073940. PubMed PMID: 24040120; PubMed Central PMCID: PMC3767662. 3

  7. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissue...

  8. Prognostic value of metastin expression in human pancreatic cancer.

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    [Background]KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. [Methods]We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tiss...

  9. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  10. Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Eishi Nagai; Masao Tanaka; Kenoki Ohuchida; Kazuhiro Mizumoto; Nami Ishikawa; Yasuhiro Ogura; Daisuke Yamada; Takuya Egami; Hayato Fujita; Seiji Ohashi

    2006-01-01

    AIM: To investigate c-met expression during early pancreatic carcinogenesis.METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real time reverse transcription-polymerase chain reaction.RESULTS: In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues.c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microdissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells (both, P < 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells.CONCLUSION: Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.

  11. Cancer in Patients With Gabapentin (GPRD)

    Science.gov (United States)

    2012-02-02

    Pain, Neuropathic; Epilepsy; Renal Pelvis Cancer; Pancreatic Cancer; Breast Cancer; Nervous System Cancer; Chronic Pancreatitis; Stomach Cancer; Renal Cell Carcinoma; Diabetes; Bladder Cancer; Bone and Joint Cancer; Penis Cancer; Anal Cancer; Cancer; Renal Cancer

  12. Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Navarrete-Muñoz, Eva M.; Wark, Petra A.; Romaguera, Dora; Bhoo-Pathy, Nirmala; Michaud, Dominique; Molina-Montes, Esther; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Katzke, Verena A.; Kühn, Tilman; Steffen, Annika; Trichopoulou, Antonia; Klinaki, Eleni; Papatesta, Eleni Maria; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Naccarati, Alessio; Mattiello, Amalia; Peeters, Petra H.; Rylander, Charlotta; Parr, Christine L.; Skeie, Guri; Weiderpass, Elisabete; Quirós, J. Ramón; Duell, Eric J.; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Wareham, Nick; Khaw, Kay Tee; Travis, Ruth C.; Key, Tim; Stepien, Magdalena; Freisling, Heinz; Riboli, Elio; Bueno-De-mesquita, H. Bas

    2016-01-01

    Background: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. Objective: We exam

  13. Sweet-beverage consumption and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

    NARCIS (Netherlands)

    Navarrete-Muñoz, Eva M.; Wark, Petra A.; Romaguera, Dora; Bhoo-Pathy, Nirmala; Michaud, Dominique; Molina-Montes, Esther; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Katzke, Verena A.; Kühn, Tilman; Steffen, Annika; Trichopoulou, Antonia; Klinaki, Eleni; Papatesta, Eleni Maria; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Naccarati, Alessio; Mattiello, Amalia; Peeters, Petra H.; Rylander, Charlotta; Parr, Christine L.; Skeie, Guri; Weiderpass, Elisabete; Quirós, J. Ramón; Duell, Eric J.; Dorronsoro, Miren; Huerta, José María; Ardanaz, Eva; Wareham, Nick; Khaw, Kay Tee; Travis, Ruth C.; Key, Tim; Stepien, Magdalena; Freisling, Heinz; Riboli, Elio; Bueno-De-mesquita, H. Bas

    2016-01-01

    Background: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. Objective: We

  14. Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Lumey, L.H.; Brants, H.A.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Background: Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis. Because insulin is secreted in response to elevated blood glucose concentrations, dietary factors that increase these concentrations may be important in pancreatic carcinogenesis. Objective: The ob

  15. Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery.

    Science.gov (United States)

    Pecorelli, N; Carrara, G; De Cobelli, F; Cristel, G; Damascelli, A; Balzano, G; Beretta, L; Braga, M

    2016-03-01

    Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer. Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by preoperative staging CT in patients undergoing pancreaticoduodenectomy for cancer. Perioperative variables and postoperative outcomes (mortality or postoperative pancreatic fistula) were collected prospectively in the institutional pancreatic surgery database. Optimal stratification was used to determine the best cut-off values for anthropometric measures. Multivariable analysis was performed to identify independent predictors of 60-day mortality and pancreatic fistula. Of 202 included patients, 132 (65·3 per cent) were classified as sarcopenic. There were 12 postoperative deaths (5·9 per cent), major complications developed in 40 patients (19·8 per cent) and pancreatic fistula in 48 (23·8 per cent). In multivariable analysis, a VFA/TAMA ratio exceeding 3·2 and American Society of Anesthesiologists grade III were the strongest predictors of mortality (odds ratio (OR) 6·76 and 6·10 respectively; both P pancreatic fistula (optimal cut-off 167 cm(2) : OR 4·05; P obesity and sarcopenia was the best predictor of postoperative death, whereas VFA was an independent predictor of pancreatic fistula. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  16. Multimodality treatment of recurrent pancreatic cancer: Mith or reality?

    Institute of Scientific and Technical Information of China (English)

    Cosimo; Sperti; Lucia; Moletta; Stefano; Merigliano

    2015-01-01

    Pancreatic adenocarcinoma is the fourth cause of cancerrelated death in the United States. Surgery is the only potentially curative treatment, but most patients present at diagnosis with unresectable or metastatic disease. Moreover, even with an R0 resection, the majority of patients will die of disease recurrence. Most recurrencesoccur in the first 2-year after pancreatic resection, and are commonly located in the abdomen, even if distant metastases can occur. Recurrent pancreatic adenocarcinoma remains a significant therapeutic challenge, due to the limited role of surgery and radiochemotherapy. Surgical management of recurrence is usually unreliable because tumor relapse typically presents as a technically unresectable, or as multifocal disease with an aggressive growth. Therefore, treatment of patients with recurrent pancreatic adenocarcinoma has historically been limited to palliative chemotherapy or supportive care. Only few data are available in the Literature about this issue, even if in recent years more studies have been published to determine whether treatment after recurrence have any effect on patients outcome. Recent therapeutic advances have demonstrated the potential to improve survival in selected patients who had undergone resection for pancreatic cancer. Multimodality management of recurrent pancreatic carcinoma may lead to better survival and quality of life in a small but significant percentage of patients; however, more and larger studies are needed to clarify the role of the different therapeutic options and the optimal way to combine them.

  17. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  18. Dynamic Contrast-Enhanced CT in Patients with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Rie Ø. Eriksen

    2016-09-01

    Full Text Available The aim of this systematic review is to provide an overview of the use of Dynamic Contrast-enhanced Computed Tomography (DCE-CT in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases to identify all relevant publications. The QUADAS-2 tool was implemented to assess the risk of bias and applicability concerns of each included study. The initial literature search yielded 483 publications. Thirteen articles were included. Articles were categorized into three groups: nine articles concerning primary diagnosis or staging, one article about tumor response to treatment, and three articles regarding scan techniques. In exocrine pancreatic tumors, measurements of blood flow in eight studies and blood volume in seven studies were significantly lower in tumor tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful in the investigation of characteristic vascular patterns of exocrine pancreatic tumors. Further clinical studies are desired for investigating the potential of DCE-CT in pancreatic tumors.

  19. l-Methionine inhibits growth of human pancreatic cancer cells

    OpenAIRE

    BENAVIDES, MAXIMO A.; BOSLAND, MAARTEN C.; da Silva, Cássio P.; Sares, Claudia T. Gomes; de Oliveira, Alana M. Cerqueira; Kemp,Rafael; dos Reis, Rodolfo B.; Martins,Vilma R.; Sampaio,Suely V.; Bland, Kirby I.; Grizzle, William E.; José S. dos Santos

    2014-01-01

    We have previously shown that l-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to l-methionine (5 mg/ml) for 7 days or for 3 days, followed by 4 days of culture without l-methionine (recovery). Cell proliferation, apoptosis, and cell cycle effects were assessed by flow cytometry after stai...

  20. Establishment of risk model for pancreatic cancer in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    Xing-Hua Lu; Li Wang; Hui Li; Jia-Ming Qian; Rui-Xue Deng; Lu Zhou

    2006-01-01

    AIM: To investigate risk factors for pancreatic cancer and establish a risk model for Han population.METHODS: This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio (ORs), 95%confidence intervals (Cis) and β value, which were further used to establish the risk model.RESULTS: According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR 1.98;95% CI 1.11-3.49, P=0.017). More importantly, heavy smokers in men had increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P=0.012)than women. Heavy alcohol drinkers (>20 cup-years)had increased risk for pancreatic cancer (OR 3.68;95%CI 1.60-8.44). Daily diet with high meat intak was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% (P= 0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its impor tance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer.CONCLUSION: Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Hah population has been established with an 88.9% sensitivity and a 97.6% specificity.

  1. Alterations of Epigenetic Regulators in Pancreatic Cancer and Their Clinical Implications

    Directory of Open Access Journals (Sweden)

    Brittany R. Silverman

    2016-12-01

    Full Text Available Pancreatic cancer is one of the most aggressive human cancer types with a five-year survival less than 7%. Emerging evidence revealed that many genetic alterations in pancreatic cancer target epigenetic regulators. Some of these mutations are driver mutations in cancer development. Several most important mechanisms of epigenetic regulations include DNA methylation, histone modifications (methylation, acetylation, and ubiquitination, chromatin remodeling, and non-coding ribonucleic acids (RNAs. These modifications can alter chromatin structure and promoter accessibility, and thus lead to aberrant gene expression. However, exactly how these alterations affect epigenetic reprogramming in pancreatic cancer cells and in different stages of tumor development is still not clear. This mini-review summarizes the current knowledge of epigenetic alterations in pancreatic cancer development and progression, and discusses the clinical applications of epigenetic regulators as diagnostic biomarkers and therapeutic targets in pancreatic cancer.

  2. Erlotinib-Induced Episcleritis in a Patient with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Armin Shahrokni

    2008-03-01

    Full Text Available Context Erlotinib is a relatively new anilinoquinazoline indicated for treatment of pancreatic cancer in combination with gemcitabine. It is a tyrosine kinase inhibitor that specifically targets epidermal growth factor receptor (EGFR, which is commonly overexpressed and/or mutated in solid tumors. Active competitive inhibition of adenosine triphosphate, inhibits downstream signal transduction of ligand dependent EGFR activation. EGFR kinase inhibitors are less toxic than conventional chemotherapy as they are relatively specific for tumor cells. Common side effects include acneiform (papulopustular rash, diarrhea, edema, pruritus, dry skin and alopecia. Case report This article reports the case of a 55-year-old Caucasian female with recurrent pancreatic cancer who developed episcleritis after seventeen days of treatment with erlotinib. Symptoms completely resolved four weeks after drug discontinuation. Conclusions To our knowledge, erlotinibinduced episcleritis has not been previously described.

  3. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

    Science.gov (United States)

    Shukla, Surendra K; Dasgupta, Aneesha; Mehla, Kamiya; Gunda, Venugopal; Vernucci, Enza; Souchek, Joshua; Goode, Gennifer; King, Ryan; Mishra, Anusha; Rai, Ibha; Nagarajan, Sangeetha; Chaika, Nina V; Yu, Fang; Singh, Pankaj K

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models.

  4. Mitochondrial uncoupling protein 2 and pancreatic cancer: a new potential target therapy.

    Science.gov (United States)

    Donadelli, Massimo; Dando, Ilaria; Dalla Pozza, Elisa; Palmieri, Marta

    2015-03-21

    Overall 5-years survival of pancreatic cancer patients is nearly 5%, making this cancer type one of the most lethal neoplasia. Furthermore, the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology. The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis, early metastasis of tumor, and resistance to almost all tested cytotoxic drugs. In this respect, the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer. Some studies have shown that the mitochondrial uncoupling protein 2 (UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues. In addition, recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming, including aerobic glycolysis stimulation, promotion of cancer progression. These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer. In this editorial, recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.

  5. Imaging the Role of Multinucleate Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in Peritoneal Metastasis in Mouse Models.

    Science.gov (United States)

    Hasegawa, Kosuke; Suetsugu, Atsushi; Nakamura, Miki; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

    2017-07-01

    The interaction between pancreatic-cancer cells and stromal cells in the tumor microenvironment (TME) is of particular importance in cancer progression and metastasis. The present report demonstrates the role of cancer-associated fibroblasts (CAFs) and multinucleate pancreatic-cancer cells in peritoneal metastasis. An orthotopic mouse model of pancreatic cancer was established with the human pancreatic cancer cell line BxPC3, which stably expresses green fluorescent protein (GFP). BxPC3-GFP cells formed peritoneal metastases by week 18 after orthotopic implantation. Using an Olympus FV1000 confocal microscope, multi-nucleated cancer cells were frequently observed in the peritoneal metastases. The primary pancreatic tumor and peritoneal-metastases were harvested, cultured and then transplanted subcutaneously. Subcutaneous tumors established from peritoneal-metastatic cells were larger than subcutaneous tumors established from primary-tumor cells. Subcutaneous tumors of each type were subsequently cultured in vitro. CAFs were observed growing out from the tumors established from peritoneal-metastatic cells, but not the tumors established from the primary cancer. The results of the present study suggest that multi-nucleated cancer cells and CAFs were related to peritoneal metastasis of pancreatic cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2015-10-01

    Major Task 4: Generate and analyze metabolites related to branched chain amino acid ( BCAA ) metabolism. 3 Major Task 4 included analyses of...branched chain amino acid ( BCAA ) catabolic products (months 10-15), quality control of data (months 16-17), and analysis of BCAA catabolic products with...pancreatic cancer development (months 18-23). We have completed measurement of BCAA catabolic products in our plasma samples and have begun the

  7. Occupational exposures and pancreatic cancer: a meta-analysis

    OpenAIRE

    Ojajarvi, I; Partanen, T.; Ahlbom, A; Boffetta, P; Hakulinen, T; Jourenkova, N.; Kauppinen, T; Kogevinas, M.; Porta, M; Vainio, H.; E. Weiderpass; Wesseling, C.

    2000-01-01

    OBJECTIVES—Consolidation of epidemiological data on pancreatic cancer and worksite exposures.
METHODS—Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Rand...

  8. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  9. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  10. New Strategies in Pancreatic Cancer: Emerging Epidemiological and Therapeutic Concepts

    OpenAIRE

    Li, Donghui; Abbruzzese, James L.

    2010-01-01

    Pancreatic cancer (PC) is a highly lethal disease with complex etiology involving both environmental and genetic factors. While cigarette smoking is known to explain 25% of cases, data from recent studies suggest that obesity and long-term type II diabetes are two major modifiable risk factors for PC. Furthermore, obesity and diabetes appear to affect the clinical outcome of patients with PC. Understanding the mechanistic effects of obesity and diabetes on the pancreas may identify new strate...

  11. Feasibility of alternating induction and maintenance chemotherapy in pancreatic cancer

    OpenAIRE

    Hann, Alexander; Bohle, Wolfram; Egger, Jan; Zoller, Wolfram

    2017-01-01

    Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic...

  12. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  13. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Adrian Thomas E

    2003-01-01

    Full Text Available Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1 our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2 the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.

  14. ROLE OF RAC-1 DEPENDENT NADPH OXIDASE IN THE GROWTH OF PANCREATIC CANCER

    OpenAIRE

    2010-01-01

    K-ras mutations occur in as high as 95% of patients with pancreatic cancer. K-ras activates Rac1-dependent NADPH oxidase, a key source of superoxide. Superoxide plays an important role in pancreatic cancer cell proliferation and scavenging or decreasing the levels of superoxide inhibits pancreatic cancer cell growth both in vitro and in vivo. DNA microarray analysis and RT-PCR has demonstrated that Rac1 is also upregulated in pancreatic cancer. The aim of this study was to determine if inhibi...

  15. Whole genomes redefine the mutational landscape of pancreatic cancer

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

  16. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  17. Pancreatic Cancer: What the Oncologist Can Offer for Palliation

    Directory of Open Access Journals (Sweden)

    Malcolm J Moore

    2002-01-01

    Full Text Available Because pancreatic cancer has a poor survival rate and only 20% of patients present with potentially resectable disease, a key goal of therapy is to provide palliation. The poor medical condition of many patients interferes with their ability to tolerate traditional chemotherapy. Recently, however, a nucleoside analogue, gemcitabine, has been developed. This drug is more effective than 5-fluorouracil (5-FU, can be used in patients who fail to respond to 5-FU and has only modest toxicity. Combination therapies including gemcitabine and other agents are being tested. Local radiotherapy seems to provide pain relief, but gastrointestinal toxicity is significant. The effect of combined modality therapy (5-FU with radiotherapy on survival is unclear, and it does not prevent local disease progression. Some novel biological agents, including angiogenesis inhibitors, matrix metalloproteinase inhibitors, antisense compounds, inhibitors of cell signalling such as epidermal growth factor and vascular endothelial growth factor, and inhibitors of oncogene activation, are undergoing phase II and III trials in patients with pancreatic cancer. Among the most promising are farnesyl protein transferase inhibitors, which modulate K-ras function. Such an approach is promising for the treatment of pancreatic cancer because this tumour frequently exhibits mutation of the ras gene.

  18. Cachexia and pancreatic cancer: are there treatment options?

    Science.gov (United States)

    Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

    2014-07-28

    Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients' outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.

  19. Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Juana; Gonzalo-Marin; Juan; Jose; Vila; Manuel; Perez-Miranda

    2014-01-01

    Endoscopic ultrasonography(EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography(CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T stagingwith less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.

  20. Leptomeningeal carcinomatosis as primary manifestation of pancreatic cancer.

    Science.gov (United States)

    Trinh, Victoria T; Medina-Flores, Rafael; Chohan, Muhammad O

    2016-08-01

    Leptomeningeal carcinomatosis (LMC) is a rare complication of cancer that often presents at an advanced stage after obvious metastasis of a primary cancer or locally advanced disease. We present an uncommon case of LMC secondary to pancreatic carcinoma presenting with headache, unilateral VII nerve palsy, and lower extremity weakness. Initial cerebrospinal fluid (CSF) studies were concerning for chronic aseptic meningitis but negative for malignant cells; the diagnosis of tuberculous meningitis was erroneously evoked. Three lumbar punctures were required to capture malignant cells. The diagnosis of LMC was based on CSF examination with cytology/immunohistochemistry and leptomeningeal enhancement on MRI. Post mortem autopsy revealed advanced and diffusely metastatic pancreatic adenocarcinoma. This patient demonstrates that solid tumors can present with leptomeningeal spread that often confuses the treating physician. Fungal or tuberculous meningitis can mimic LMC in the absence of neoplastic signs and negative CSF cytology. This event is exceedingly rare in pancreatic cancer. If the index of suspicion is high, repeat CSF sampling can increase the sensitivity of detection of malignant cells and thus result in the correct diagnosis.

  1. Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin.

    Science.gov (United States)

    Xu, Xiao Dong; Zhao, Yan; Zhang, Min; He, Rui Zhi; Shi, Xiu Hui; Guo, Xing Jun; Shi, Cheng Jian; Peng, Feng; Wang, Min; Shen, Min; Wang, Xin; Li, Xu; Qin, Ren Yi

    2017-02-10

    Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

  2. Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin

    Science.gov (United States)

    Xu, Xiao Dong; Zhao, Yan; Zhang, Min; He, Rui Zhi; Shi, Xiu Hui; Guo, Xing Jun; Shi, Cheng Jian; Peng, Feng; Wang, Min; Shen, Min; Wang, Xin; Li, Xu; Qin, Ren Yi

    2017-01-01

    Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer. PMID:28208617

  3. Kaempferol Inhibits Pancreatic Cancer Cell Growth and Migration through the Blockade of EGFR-Related Pathway In Vitro

    OpenAIRE

    Jungwhoi Lee; Jae Hoon Kim

    2016-01-01

    Pancreatic cancer is one of the most appalling cancers with a pessimistic prognosis. Despite many therapies, there has been no improvement of survival rates. In this study, we assessed the anti-cancer effects of kaempferol, a well known flavonoid having functional bio-activity against various malignant tumors. Kaempferol had anti-cancer effects on Miapaca-2, Panc-1, and SNU-213 human pancreatic cancer cells. In a dose-dependent manner, kaempferol decreased viability of these pancreatic cancer...

  4. [New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

    Science.gov (United States)

    Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry

    2016-01-01

    This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

  5. Chronic Pancreatitis, Type 3c Diabetes, and Pancreatic Cancer Risk

    Directory of Open Access Journals (Sweden)

    David C Whitcomb

    2014-09-01

    Full Text Available About half of all patients with chronic pancreatitis (CP develop diabetes mellitus (DM due to the loss of islet cell mass, not just beta cells as in Type 1 DM (T1DM, or due to insulin resistance, as in Type 2 DM (T2DM. Patients with DM from loss of islets due to pancreatic disease or resection are diagnosed with pancreatogenic or Type 3c DM (T3cDM. Patients with T3cDM also lose counter-regulatory hormones, such as glucagon and pancreatic polypeptide, and experience maldigestion associated with pancreatic exocrine insufficiency. Patients with T3cDM are therefore more susceptible to hypoglycemia and a mismatch (asynchrony between food ingestion and nutrient absorption. At the same time, the use of incretin therapy is likely useless, since maldigestion leads to the release of higher levels of hind gut hormones, including GLP1. Thus, T3cDM caused by CP or destruction of the islets involves a special class of potential risks and comorbidity that may be overlooked if the CP has not been diagnosed.

  6. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines.

    Science.gov (United States)

    Joseph, Immanual; Tressler, Robert; Bassett, Ekaterina; Harley, Calvin; Buseman, Christen M; Pattamatta, Preeti; Wright, Woodring E; Shay, Jerry W; Go, Ning F

    2010-11-15

    Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy.

  7. Statins and Cancer Prevention

    Science.gov (United States)

    ... Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  8. Diethylstilbestrol (DES) and Cancer

    Science.gov (United States)

    ... Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  9. Secondhand Smoke and Cancer

    Science.gov (United States)

    ... Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  10. Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report.

    Science.gov (United States)

    Hine, R Jean; Srivastava, Sudhir; Milner, John A; Ross, Sharon A

    2003-11-01

    Adenocarcinoma of the pancreas is one of most catastrophic and least understood of cancers. Evidence from clinical studies indicates that the development of pancreas cancer progresses over many years before symptoms appear. Most people with pancreatic cancer die within six months of diagnosis. The lack of early disease markers, the paucity of direct subject/patient interview data and limited availability of high quality biological samples have slowed progress toward identifying environmental and genetic disease risk factors. Much remains to be learned about the development of pancreatic cancer and about potential interventions for disease prevention. Epidemiological and mechanistic studies examining risk factors for pancreatic cancer supply little consistent or strong evidence to provide a cohesive prevention strategy for this cancer, but offer clues for future research concerning the prevention and early detection of this devastating disease. This Executive Summary provides background discussion on pancreatic cancer and summaries of each of the topics discussed at the workshop, including 1) Molecular aspects, 2) Dietary and other risk factors for pancreatic cancer, 3) The metabolic hypothesis for pancreatic cancer, 4) Preclinical studies on pancreatic cancer, 5) Methylation, 6) Oxidative stress and 7) Biomarker Profiling. This document also contains a compilation of recommendations for future research, concluding remarks, a list of speakers and participants attending the workshop, and a selection of key references to aid future research into nutritional links to mechanisms underlying pancreas cancer. The recommendations section suggests gaps in current knowledge and articulates future directions for this area of investigation.

  11. Celiac plexus neurolysis in the management of unresectable pancreatic cancer: When and how?

    Science.gov (United States)

    Wyse, Jonathan M; Chen, Yen-I; Sahai, Anand V

    2014-01-01

    Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20% resectability at diagnosis, and overall 5-year survival of 5%. Pain is common in pancreatic cancer patients with 70%-80% suffering substantial pain. Celiac plexus neurolysis (CPN) is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption. CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia. This review sets out to explore the current status of CPN in non-resectable pancreatic cancer. We will examine: (1) the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN; (2) specific technique modifications including bilateral (vs central) injections and celiac ganglia neurolysis; and (3) the issue of CPN timing, early at pancreatic cancer diagnosis vs traditional late use as salvage therapy. PMID:24605017

  12. A transcriptome analysis by lasso penalized Cox regression for pancreatic cancer survival.

    Science.gov (United States)

    Wu, Tong Tong; Gong, Haijun; Clarke, Edmund M

    2011-12-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the United States with five-year survival rates less than 5% due to rare detection in early stages. Identification of genes that are directly correlated to pancreatic cancer survival is crucial for pancreatic cancer diagnostics and treatment. However, no existing GWAS or transcriptome studies are available for addressing this problem. We apply lasso penalized Cox regression to a transcriptome study to identify genes that are directly related to pancreatic cancer survival. This method is capable of handling the right censoring effect of survival times and the ultrahigh dimensionality of genetic data. A cyclic coordinate descent algorithm is employed to rapidly select the most relevant genes and eliminate the irrelevant ones. Twelve genes have been identified and verified to be directly correlated to pancreatic cancer survival time and can be used for the prediction of future patient's survival.

  13. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Michael Hocke; Ewald Schulze; Peter Gottschalk; Theodor Topalidis; Christoph F Dietrich

    2006-01-01

    AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels.METHODS: In 86 patients with suspected chronic pancreatitis (age: 62±12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endoscopic B-mode, power Doppler ultrasound and contrastenhanced power mode (Hitachi EUB 525, SonoVue(R), 2.4mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue(R) contrastenhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology,operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue(R), regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue(R) and detection of arterial and venous vessels.RESULTS: The sensitivity and specificity of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3%in 28 of 30 patients with chronic inflammatory pancreatic disease.CONCLUSION: Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.

  14. SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells.

    Science.gov (United States)

    Jin, Jianguang; Chu, Zhijie; Ma, Pengfei; Meng, Yuanpu; Yang, Yanhui

    2017-03-01

    SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.

  15. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

    Science.gov (United States)

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-01

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future. PMID:28134290

  16. Focused ultrasound induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    GUO Qian; JIANG Li-xin; HU Bing

    2012-01-01

    Background The incidence and mortality rate of pancreatic cancer have increased dramatically in China over recent decades.Focused ultrasound (FU) has been somewhat successful in treating pancreatic cancer.The purpose of this study was to investigate apoptosis in pancreatic cancer cells induced by FU.Methods Suspension of human pancreatic carcinoma cell line PaTu 8988t was radiated by FU,using five doses with different radiation parameters and patterns,including one blank control.Temperature increase of the cell suspension was monitored.Cell apoptosis and death after FU radiation was observed using fluorescence microscopy and was tested by flow cytometer at 3,6,12,24,and 48 hours after ultrasound radiation.Results The maximum cell suspension temperatures following five radiation doses were 28°C,(42.20±2.17)°C,(50.80±0.84)°C,(55.80±2.17)°C,and (65.20±3.11)°C; differences between the doses were statistically significant (P <0.05).The apoptosis rate peaked at 24 hours after radiation,at (0.56±0.15)%,(1.28±0.16)%,(1.84±0.29)%,(5.74±1.15)%,and (2.00±0.84)% for the five doses; differences between the doses were statistically significant (P <0.05).Between doses 1-4,cell apoptosis rates increased as the Tmax increased.In dose 5,as the Tmax was above 60°C,the apoptosis rate decreased.Conclusion Sub-threshold thermal exposures of FU radiation with a continuous radiation pattern could result in higher oercentage of apoptosed cells.

  17. Serum cytokine profile in patients with pancreatic cancer.

    Science.gov (United States)

    Torres, Carolina; Perales, Sonia; Alejandre, María José; Iglesias, José; Palomino, Rogelio J; Martin, Miguel; Caba, Octavio; Prados, José C; Aránega, Antonia; Delgado, Juan R; Irigoyen, Antonio; Ortuño, Francisco M; Rojas, Ignacio; Linares, Ana

    2014-10-01

    Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer. A cytokine antibody array was performed to simultaneously identify 507 cytokines in sera of patients with pancreatic cancer and healthy controls. The nonparametric Mann-Whitney U test was used to pairwise compare the controls, the pretreated patients, and the posttreated patients. Fold changes greater than or equal to 1.5 or less than or equal to 1/1.5 were considered significant. Receiver operating characteristic curves were used to assess the performance of the model. A leave-one-out cross-validation was used for estimating prediction error. Comparing the sera of pretreated patients against the control samples, the cytokines fibroblast growth factor 10 (FGF-10/keratinocyte growth factor-2 (KGF-2), chemokine (C-X-C motif) ligand 11 interferon inducible T cell alpha chemokine (I-TAC)/chemokine [C-X-C motif] ligand 11 (CXCL11), oncostatin M (OSM), osteoactivin/glycoprotein nonmetastatic melanoma protein B, and stem cell factor (SCF) were found significantly overexpressed. Besides, the cytokines CD30 ligand/tumor necrosis factor superfamily, member 8 (TNFSF8), chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF were differentially expressed in response to treatment. We propose a role for FGF-10/KGF-2, I-TAC/CXCL11, OSM, osteoactivin/glycoprotein nonmetastatic melanoma protein B, and SCF as novel diagnostic biomarkers. CD30 ligand/TNFSF8, chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF might represent as predictive biomarkers for gemcitabine and erlotinib response of patients with pancreatic cancer.

  18. Dendritic cell-based vaccine for pancreatic cancer in Japan

    Institute of Scientific and Technical Information of China (English)

    Masato Okamoto; Masanori Kobayashi; Yoshikazu Yonemitsu; Shigeo Koido; Sadamu Homma

    2016-01-01

    "Vaccell" is a dendritic cell(DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity(DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide(WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide(WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and-Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

  19. Serum level of TSGF,CA242 and CA19-9 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Hai-Feng Deng; Ming-Yang Lu; Jun Wu; Hong-Yu Zhang; Wen-Hui Sun; Mei Ji

    2004-01-01

    AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer.METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients.RESULTS: The positive likelihood ratios of TSGF, CA242and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17,respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0%and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9.CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking.There is very important correlation between the three markers and the pancreatic cancer.

  20. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  1. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Science.gov (United States)

    Fillat, Cristina; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano

    2011-01-01

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed. PMID:24212620

  2. Relevance of Educational Factors in the Treatment of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Dan Silviu VERZEA

    2012-04-01

    Full Text Available Introduction: radical pancreatic resections are the only chance to cure a pancreatic cancer, if the tumor is in an early stage of development. The results of the surgical teams have constantly improved in time, in terms of survival and a good quality of life. Unfortunately, only a small part of the patients benefit from surgical interventions. The causes of this phenomenon are complex, educational factors playing an important role. Material and Methods: 44 patients with pancreatoduodenectomy, operated between 2005 and 2008 were divided in 2 groups. Several parameters were recorded, including age, sex, level of education and place of origin, associated diabetes mellitus, these being studied in relation with the postoperative morbidity and mortality. Results: the morbidity after operation was 65,90%, and the mortality – 6,81%. The level of education, age, socioeconomic status, the presence of diabetes mellitus did not significantly influence the morbidity and the mortality after pancreatoduodenectomy. Conclusions: the postoperative morbidity and mortality are more incidental in small medical centers, but their values are acceptable, if compared with the data from the literature. Excluding the potential patients candidates for radical surgery because they are old or they have poor economic status is not a justified attitude. Education of the patients, medical stuff and surgeons is very important and it can raise the number of healed cases and could change the perception on pancreatic cancer.

  3. Gemcitabine in elderly patients with advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Olivia Hentic; Chantal Dreyer; Vinciane Rebours; Magaly Zappa; Philippe Lévy; Eric Raymond; Philippe Ruszniewski; Pascal Hammel

    2011-01-01

    AIM: To assess feasibility, tolerability and efficacy of gemcitabine-based chemotherapy in patients ≥ 75 years old with advanced pancreatic cancer. METHODS: All consecutive patients ≥ 75 years old with advanced pancreatic adenocarcinoma were included in this retrospective study. Necessary criteria to receive chemotherapy were: performance status 0-2, adequate biological parameters and no serious comorbidities. Other patients received best supportive care (BSC). RESULTS: Thirty-eight patients (53% women, median age 78 years, range 75-84) with pancreatic cancer (metastatic: n = 20, locally advanced: n = 18) were studied. Among them, 30 (79%) were able to receive chemotherapy [median number: 9 infusions (1-45)]. Six patients (23%) had at least one episode of grade 3 neutropenia and one patient developed a grade 3 hemolytic-uremic syndrome. No toxic death occurred. Three patients (11%) had a partial tumor response, 13 (46%) had a stable disease and 12 (43%) had a tumor progression. Median survival was 9.1 mo (metastatic: 6.9 mo, locally advanced: 11.4 mo). CONCLUSION: Tolerance and efficacy of gemcitabinebased chemotherapy is acceptable in elderly patients in good condition, with similar results to younger patients.

  4. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi

    2011-01-01

    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  5. File list: NoD.Pan.10.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Pan.10.AllAg.Pancreatic_cancer_cells mm9 No description Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Pan.10.AllAg.Pancreatic_cancer_cells.bed ...

  6. File list: InP.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.05.AllAg.Pancreatic_cancer_cells mm9 Input control Pancreas Pancreatic canc...er cells SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  7. [Tumor markers in the diagnosis of pancreatic cancer].

    Science.gov (United States)

    Cappelli, G; Paladini, S; D'Agata, A

    1999-01-01

    The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The gangliosides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a "triplet" of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an "integrated" use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of radiochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.

  8. Plasma cotinine levels and pancreatic cancer in the EPIC cohort study

    NARCIS (Netherlands)

    Leenders, Max; Chuang, Shu-Chun; Dahm, Christina C.; Overvad, Kim; Ueland, Per Magne; Midttun, Oivind; Vollset, Stein Emil; Tjonneland, Anne; Halkjaer, Jytte; Jenab, Mazda; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Canzian, Federico; Boeing, Heiner; Weikert, Cornelia; Trichopoulou, Antonia; Bamia, Christina; Naska, Androniki; Palli, Domenico; Pala, Valeria; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; van Duijnhoven, Franzel J. B.; Peeters, Petra H. M.; van Gils, Carla H.; Lund, Eiliv; Rodriguez, Laudina; Duell, Eric J.; Sanchez Perez, Maria-Jose; Molina-Montes, Esther; Huerta Castano, Jose Maria; Barricarte, Aurelio; Larranaga, Nerea; Johansen, Dorthe; Lindkvist, Bjorn; Sund, Malin; Ye, Weimin; Khaw, Kay-Tee; Wareham, Nicholas J.; Michaud, Dominique S.; Riboli, Elio; Xun, Wei W.; Allen, Naomi E.; Crowe, Francesca L.; Bueno-de-Mesquita, H. Bas; Vineis, Paolo

    2012-01-01

    Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective

  9. Prediction of Candidate Drugs for Treating Pancreatic Cancer by Using a Combined Approach.

    Directory of Open Access Journals (Sweden)

    Yanfen Ma

    Full Text Available Pancreatic cancer is the leading cause of death from solid malignancies worldwide. Currently, gemcitabine is the only drug approved for treating pancreatic cancer. Developing new therapeutic drugs for this disease is, therefore, an urgent need. The C-Map project has provided a wealth of gene expression data that can be mined for repositioning drugs, a promising approach to new drug discovery. Typically, a drug is considered potentially useful for treating a disease if the drug-induced differential gene expression profile is negatively correlated with the differentially expressed genes in the target disease. However, many of the potentially useful drugs (PUDs identified by gene expression profile correlation are likely false positives because, in C-Map, the cultured cell lines to which the drug is applied are not derived from diseased tissues. To solve this problem, we developed a combined approach for predicting candidate drugs for treating pancreatic cancer. We first identified PUDs for pancreatic cancer by using C-Map-based gene expression correlation analyses. We then applied an algorithm (Met-express to predict key pancreatic cancer (KPC enzymes involved in pancreatic cancer metabolism. Finally, we selected candidates from the PUDs by requiring that their targets be KPC enzymes or the substrates/products of KPC enzymes. Using this combined approach, we predicted seven candidate drugs for treating pancreatic cancer, three of which are supported by literature evidence, and three were experimentally validated to be inhibitory to pancreatic cancer celllines.

  10. Active and passive smoking and the risk of pancreatic cancer in the Netherlands cohort study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2010-01-01

    Background: To date, cigarette smoking is the most consistent risk factor for pancreatic cancer. We prospectively examined the role of active cigarette smoking, smoking cessation, and passive smoking as determinants for pancreatic cancer. Methods: The Netherlands Cohort Study consisted of 120,852

  11. Anthropometry and pancreatic cancer risk: An illustration of the importance of microscopic verification

    NARCIS (Netherlands)

    Verhage, B.A.J.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2007-01-01

    Using data collected of a large population-based cohort study, we studied the association between anthropometric factors and the risk of pancreatic cancer. Furthermore, we investigated whether these associations differ among microscopically confirmed pancreatic cancer (MCPC) cases and non-MCPC

  12. Blood coagulation-(in)dependent protease activated receptor signaling in pancreatic cancer

    NARCIS (Netherlands)

    K. Shi

    2015-01-01

    There is no doubt that pancreatic cancer is one of the most lethal diseases in general and current treatment options are limited. The studies described in this thesis pinpoint Protease activated receptors (PARs) as key players in pancreatic cancer progression. Inhibition of PAR-1 may be clinical rel

  13. Plasma cotinine levels and pancreatic cancer in the EPIC cohort study

    NARCIS (Netherlands)

    Leenders, M.; Chuang, S.C.; Dahm, C.C.; Overvad, K.; Ueland, P.M.; Midttun, O.; Vollset, S.E.; Tjonneland, A.; Halkjaer, J.; Jenab, M.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Kaaks, R.; Canzian, F.; Boeing, H.; Weikert, C.; Trichopoulou, A.; Bamia, C.; Naska, A.; Palli, D.; Pala, V.; Mattiello, A.; Tumino, R.; Sacerdote, C.; Duijnhoven, F.J.B. van; Peeters, P.H.M.; Gils, C.H. van; Lund, E.; Rodriguez, L.; Duell, E.J.; Perez, M.J.; Molina-Montes, E.; Castano, J.M.; Barricarte, A.; Larrañaga, N.; Johansen, D.; Lindkvist, B.; Sund, M.; Ye, W.; Khaw, K.T.; Wareham, N.J.; Michaud, D.S.; Riboli, E.; Xun, W.W.; Allen, N.E.; Crowe, F.L.; Bueno-De-Mesquita, H.B.; Vineis, P.

    2012-01-01

    Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective

  14. Dairy products and pancreatic cancer risk: A pooled analysis of 14 cohort studies

    NARCIS (Netherlands)

    Genkinger, J.M.; Wang, M.; Li, R.; Albanes, D.; Anderson, K.E.; Bernstein, L.; Brandt, P.A. van den; English, D.R.; Freudenheim, J.L.; Fuchs, C.S.; Gapstur, S.M.; Giles, G.G.; Goldbohm, R.A.; Håkansson, N.; Horn-Ross, P.L.; Koushik, A.; Marshal, J.R.; McCullough, M.L.; Miller, A.B.; Robien, K.; Rohan, T.E.; Schairer, C.; Silverman, D.T.; Stolzenberg-Solomon, R.Z.; Virtamo, J.; Willett, W.C.; Wolk, A.; Ziegler, R.G.; Smith-Warner, S.A.

    2014-01-01

    Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy produc

  15. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

  16. Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop.

    Science.gov (United States)

    Andersen, Dana K; Andren-Sandberg, Åke; Duell, Eric J; Goggins, Michael; Korc, Murray; Petersen, Gloria M; Smith, Jill P; Whitcomb, David C

    2013-11-01

    A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article.

  17. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis.

    Science.gov (United States)

    Karagianni, Vasiliki Th; Papalois, Apostolos E; Triantafillidis, John K

    2012-12-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance of the nutritional and functional status and the prevention or attenuation of cachexia. Oral nutrition could reduce complications while restoring quality of life. Enteral nutrition in the post-operative period could also reduce infective complications. The evidence for immune-enhanced feed in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported by the available clinical data. Nutritional support during the post-operative period on a cyclical basis is preferred because it is associated with low incidence of gastric stasis. Postoperative total parenteral nutrition is indicated only to those patients who are unable to be fed orally or enterally. Thus nutritional deficiency is a relatively widesoread and constant finding suggesting that we must optimise the nutritional status both before and after surgery.

  18. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Helmut Friess

    2011-02-01

    Full Text Available Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis, the prophylactic creation of a gastro-intestinal bypass (double bypass is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

  19. First-Line Treatment of Metastatic Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Mohammed Tokh

    2012-03-01

    Full Text Available Metastatic pancreatic cancer is an aggressive malignancy that is difficult to treat. Gemcitabine monotherapy has been used first line and many contemporary treatment approaches have focused on gemcitabine plus experimental agents. The 2012 ASCO Gastrointestinal Cancers Symposium Abstract #213 is a study of gemcitabine with IPI-926, a novel hedgehog pathway inhibitor. Abstract #227 is a study of gemcitabine with 90Y-hPAM4 radioimmunotherapy with yttrium labeled anti-mucin humanized antibody. Abstract #296 is a study of gemcitabine with temsirolimus, an mTOR inhibitor. Gemcitabine and erlotinib has shown slight advantages to gemcitabine alone. Abstract #253 takes this one step further and evaluates gemcitabine and erlotinib with apricoxib, a COX-2 inhibitor. FOLFIRINOX has shown superiority to gemcitabine; however, doing so at the cost of significantly greater toxicity. Abstract #199, is a study which examines the cost effectiveness of first line FOLFIRINOX approaches. Another cost effective study is portrayed in Abstract #372, a study evaluating the survival of unresectable pancreatic cancer patients treated with gemcitabine and the disease course is followed clinically without radiographic follow-up.

  20. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut, E-mail: friess@chir.med.tu-muenchen.de [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, D-81675 Munich (Germany)

    2011-02-14

    Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

  1. Potential New Pharmacological Agents Derived From Medicinal Plants for the Treatment of Pancreatic Cancer.

    Science.gov (United States)

    Azimi, Haniye; Khakshur, Ali Asghar; Abdollahi, Mohammad; Rahimi, Roja

    2015-01-01

    In the present article, we reviewed plants and phytochemical compounds demonstrating beneficial effects in pancreatic cancer to find new sources of pharmaceutical agents. For this purpose, Scopus, PubMed, Web of Science, and Google scholar were searched for plants or herbal components with beneficial effects in the treatment of pancreatic cancer. Data were collected up to January 2013. The search terms were "plant," "herb," "herbal therapy," or "phytotherapy" and "pancreatic cancer" or "pancreas." All of the human in vivo and in vitro studies were included. According to studies, among diverse plants and phytochemicals, 12 compounds including apigenin, genistein, quercetin, resveratrol, epigallocatechin gallate, benzyl isothiocyanate, sulforaphane, curcumin, thymoquinone, dihydroartemisinin, cucurbitacin B, and perillyl alcohol have beneficial action against pancreatic cancer cells through 4 or more mechanisms. Applying their plausible synergistic effects can be an imperative approach for finding new efficient pharmacological agents in the treatment of pancreatic cancer.

  2. Obesity and the risk of pancreatic cancer: an italian multicenter study.

    Science.gov (United States)

    Pezzilli, Raffaele; Morselli-Labate, Antonio Maria; Migliori, Marina; Manca, Marco; Bastagli, Luciana; Gullo, Lucio

    2005-10-01

    The purpose of this work was to determine whether obesity is a risk factor for pancreatic cancer. We studied 400 patients with this tumor and 400 controls matched for sex and age from various Italian cities. We used a standardized questionnaire that was compiled at personal interview, with particular attention to body weight at the time of the interview, and for those with the tumor, their weight before onset of the disease. Body mass index (BMI) was calculated as the patient's weight in kilograms divided by their height in meters squared. The risk of pancreatic cancer adjusted for smoking was 5-fold higher (P pancreatic cancer, whereas no significant relationship was found between BMI classes and the risk of pancreatic cancer (P = 0.984). These findings indicate that obesity is not a risk factor for pancreatic cancer.

  3. Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic.Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However, the response rates have been highly variable, and are often irreproducible. To improve this low response rate, various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug, generating higher local drug concentrations in tumor cells with lower toxicity.Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and, simultaneously, a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

  4. Expression of Survivin in pancreatic cancer and its correlation to expression of Bcl-2

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Qiao; Yu-Qing Zhang; Yu-Chun Yin; Zui Tan

    2004-01-01

    AIM: To investigate the expression of Survivin in pancreatic cancer and its correlation to the expression of Bcl-2.METHODS: Survivin and Bcl-2 expressions were examined by immunohistochemistry in 42 tissue samples from pancreatic cancer and 10 from normal pancrease. RESULTS: No survivin expression was detected in the tissue samples from normal pancrease, while it was detected in 34 of 42 tissue samples from pancreatic cancer (81.95%).There was a correlation between survivin expression and differentiation and stages of pancreatic cancer. Survivin positive cases were strongly correlated to Bcl-2 expression (28/30 vs 6/12, P<0.05).CONCLUSION: Overexpression of survivin plays an important role in the development and progression of pancreatic cancer, and correlates to the expression of Bcl-2. Survivin expression can be used as a prognostic factor.

  5. Receptivity and preferences of pancreatic cancer family members for participating in lifestyle programs to reduce cancer risk

    OpenAIRE

    Howell, Lisa A.; Sinicrope, Pamela S.; Brockman, Tabetha A.; Patten, Christi A.; Decker, Paul A; Ehlers, Shawna L.; Nadeau, Ashley; Rabe, Kari G.; Breitkopf, Carmen Radecki; Gloria M Petersen

    2013-01-01

    Background Cancer is a shared family experience that might provide an opportunity for lifestyle change among at-risk family members. The purpose of this study was to assess receptivity and preferences for cancer risk reduction programs among at-risk family members with two or more relatives affected with pancreas cancer. Methods We surveyed 401 at-risk family members in an existing pancreatic cancer family registry. Participants completed a mailed survey which examined demographic, medical, a...

  6. Noninvasive radiofrequency treatment effect on mitochondria in pancreatic cancer cells.

    Science.gov (United States)

    Curley, Steven A; Palalon, Flavio; Lu, Xiaolin; Koshkina, Nadezhda V

    2014-11-01

    The development of novel therapeutic approaches for cancer therapy is important, especially for tumors that have poor response or develop resistance to standard chemotherapy and radiation. We discovered that noninvasive radiofrequency (RF) fields can affect cancer cells but not normal cells, inhibit progression of tumors in mice, and enhance the anticancer effects of chemotherapy. However, it remains unclear what physiological and molecular mechanisms this treatment induces inside cells. Here, we studied the effect of RF treatment on mitochondria in human pancreatic cancer cells. The morphology of mitochondria in cells was studied via electron microscopy. The alteration of mitochondrial membrane potential (Δψ) was accessed using a Mitotracker probe. The respiratory activity of mitochondria was evaluated by analyzing changes in oxygen consumption rates determined with a Mito Stress Test Kit. The production of intracellular reactive oxygen species was performed using flow cytometry. The colocalization of mitochondria and autophagosome markers in cells was performed using fluorescence immunostaining and confocal microscopy analysis. RF fields treatment changed the morphology of mitochondria in cancer cells, altered polarization of the mitochondrial membrane, substantially impaired mitochondrial respiration, and increased reactive oxygen species production, indicating RF-induced stress on the mitochondria. We also observed frequent colocalization of the autophagosome marker LC3B with the mitochondrial marker Tom20 inside cancer cells after RF exposure, indicating the presence of mitochondria in the autophagosomes. This suggests that RF-induced stress can damage mitochondria and induce elimination of damaged organelles via autophagy. RF treatment impaired the function of mitochondria in cancer cells. Therefore, mitochondria can represent one of the targets of the RF treatment. © 2014 American Cancer Society.

  7. Vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice.The standard chemotherapy of pancreatic cancer has been gemcitabine,but the response rate is low.Therefore,it is in urgent need to explore an effective clinical therapy for this cancer.This paper,a case report,is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer.Methods A 52-year-old female pati...

  8. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells.

    OpenAIRE

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke; Novak, Ivana

    2016-01-01

    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro a...

  9. Helicobacter species ribosomal DNA in the pancreas, stomach and duodenum of pancreatic cancer patients

    Institute of Scientific and Technical Information of China (English)

    Hans-Olof Nilsson; Unne Stenram; Ingemar Ihse; Torkel Wadstr(o)m

    2006-01-01

    AIM: To determine whether gastric and enteric Helico-bacter species are associated with pancreatic cancer.METHODS: Patients with exocrine pancreatic cancer(n = 40), neuroendocrine cancer (n = 14), multipleendocrine neoplasia type 1 (n = 8), and chronic pan-creatitis (n = 5) were studied. Other benign pancreat-ic diseases (n = 10) and specimens of normal pancre-as (n = 7) were included as controls. Pancreatic tissuespecimens were analyzed by Helicobacter-specificPCR-assay and products were characterized by dena-turing gradient electrophoresis and DNA-sequencing.From a subset of the pancreatic cancer patients, gas-tric and/or duodenal tissue as well as gallbladder andductus choledochus tissue were analyzed. Gallbladderand choledochus samples were included as controls.Stomach and duodenum samples were investigated toanalyze whether a gastric helicobacter might dissemi-nate to the pancreas in pancreatic cancer patients.Pancreatic specimens were analyzed by Bacteroides-specific PCR for detecting the translocation of indig-enous gut microbes to the diseased pancreas.RESULTS: Helicobacter DNA was detected in pancreas(tumor and/or surrounding tissue) of 75% of patientswith exocrine cancer, 57% of patients with neuro-endocrine cancer, 38% of patients with multiple eh-docrine neoplasia, and 60% of patients with chronicpancreatitis. All samples from other benign pancreaticdiseases and normal pancreas were negative. Thirty-three percent of the patients were helicobacter-positive in gastroduodenal specimens. Surprisingly,H. bilis was identified in 60% of the positive gastro-duodenal samples. All gallbladder and ductus cho-ledochus specimens were negative for helicobacter.Bacteroides PCR-assay was negative for all pancreaticsamples.CONCLUSION: Helicobacter DNA commonly detectedin pancreatic cancer suggests a possible role of theemerging pathogens in the development of chronicpancreatitis and pancreatic cancer.

  10. Pancreatic Cancer, A Mis-interpreter of the Epigenetic Language.

    Science.gov (United States)

    Iguchi, Eriko; Safgren, Stephanie L; Marks, David L; Olson, Rachel L; Fernandez-Zapico, Martin E

    2016-12-01

    Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management. Over the past two decades, a model has been advanced of PDAC initiation and progression as a multi-step process driven by the acquisition of mutations leading to loss of tumor suppressors and activation of oncogenes. The recognition of the essential roles of these genetic alterations in the development of PDAC has revolutionized our knowledge of this disease. However, none of these findings have turned into effective treatment for this dismal malignancy. In recent years, studies in the areas of chromatin modifications, and non-coding RNAs have uncovered mechanisms for regulating gene expression which occur independently of genetic alterations. Chromatin-based mechanisms are interwoven with microRNA-driven regulation of protein translation to create an integrated epigenetic language, which is grossly dysregulated in PDAC. Thus in PDAC, key tumor suppressors that are well established to play a role in PDAC may be repressed, and oncogenes can be upregulated secondary to epigenetic alterations. Unlike mutations, epigenetic changes are potentially reversible. Given this feature of epigenetic mechanisms, it is conceivable that targeting epigenetic-based events promoting and maintaining PDAC could serve as foundation for the development of new therapeutic and diagnostic approaches for this disease.

  11. MUC1 Regulates PDGFA Expression During Pancreatic Cancer Progression

    Science.gov (United States)

    Sahraei, Mahnaz; Roy, Lopamudra Das; Curry, Jennifer M; Teresa, Tinder L; Nath, Sritama; Besmer, Dahlia; Kidiyoor, Amritha; Dalia, Ritu; Gendler, Sandra J; Mukherjee, Pinku

    2012-01-01

    Pancreatic Ductal Adenocarcinoma (PDA) has one of the worst prognoses of all cancers. Mucin 1 (MUC1), a transmembrane mucin glycoprotein, is a key modulator of several signaling pathways that affect oncogenesis, motility, and metastasis. Its expression is known to be associated with poor prognosis in patients. However, the precise mechanism remains elusive. We report a novel association of MUC1 with Platelet-Derived Growth Factor-A (PDGFA). PDGFA is one of the many drivers of tumor growth, angiogenesis, and metastasis in PDA. Using mouse PDA models as well as human samples, we show clear evidence that MUC1 regulates the expression and secretion of PDGFA. This, in turn, influences proliferation and invasion of pancreatic cancer cells leading to higher tumor burden in vivo. In addition, we reveal that MUC1 over expressing cells are heavily dependent on PDGFA both for proliferation and invasion while MUC1-null cells are not. Moreover, PDGFA and MUC1 are critical for translocation of βcatenin to the nucleus for oncogenesis to ensue. Finally, we elucidate the underlying mechanism by which MUC1 regulates PDGFA expression and secretion in pancreatic cancer cells. We show that MUC1 associates with Hif1-α, a known transcription factor involved in controlling PDGFA expression. Furthermore, MUC1 facilitates Hif1-α translocation to the nucleus. In summary, we have demonstrated that MUC1-induced invasion and proliferation occurs via increased exogenous production of PDGFA. Thus, impeding MUC1 regulation of PDGFA signaling may be therapeutically beneficial for patients with PDA. PMID:22266848

  12. Are risk factors associated with outcomes in pancreatic cancer?

    Directory of Open Access Journals (Sweden)

    De-shen Wang

    Full Text Available BACKGROUND: The development of pancreatic cancer is a process in which genes interact with environmental factors. We performed this study to determine the effects of the ABO blood group, obesity, diabetes mellitus, metabolic syndrome (MetS, smoking, alcohol consumption and hepatitis B viral (HBV infection on patient survival. METHODS: A total of 488 patients with pancreatic cancer were evaluated. RESULT: Patients who presented as chronic carriers of HBV infection were younger at disease onset (p = 0.001 and more predominantly male (p = 0.020 than those never exposed to HBV. Patients with MetS had later disease staging (p = 0.000 and a lower degree of pathological differentiation (p = 0.008 than those without MetS. In a univariate analysis, the ABO blood group, smoking and alcohol consumption were not associated with overall survival. HBsAg-positivity and elevated fasting plasma glucose were significantly associated with unfavorable survival though not in the multivariate analysis. The presence of MetS (HR: 1.541, 95% CI: 1.095-2.169, p = 0.013, age ≥65, an elevated CA19-9 baseline level, TNM staging, the type of surgery, the degree of differentiation and chemotherapy were independently associated with overall survival. CONCLUSION: We report, for the first time, that patients with chronic HBV infection may represent a special subtype of pancreatic cancer, who have a younger age of disease onset and male dominancy. Patients with MetS had later disease staging and a poorer histological grade. Patients with MetS demonstrated significantly poorer survival.

  13. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  14. Imaging Pancreatic Cancer Using Bioconjugated InP Quantum Dots

    OpenAIRE

    2009-01-01

    In this paper, we report the successful use of non-cadmium based quantum dots (QDs) as highly efficient and non-toxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulphide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in non-aqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjug...

  15. Pancreatic cancer with a high serum IgG4 concentration

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Pong Yui Chen; Yuyang Tu; Hitoshi Nakajima; Naoto Egawa; Kouji Tsuruta; Atsutake Okamoto; Tsunekazu Hishima

    2006-01-01

    Differentiation between autoimmune pancreatitis and pancreatic cancer is sometimes difficult. It has been reported that serum IgG4 concentrations are significantly elevated and particularly high (>135 mg/dL) in autoimmune pancreatitis. Measurement of serum IgG4 has become a useful tool for differentiating between autoimmune pancreatitis and pancreatic cancer. However,we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL) who underwentpancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4 levels continued after the resection. On histology, adenocarcinoma of the pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the lower bile duct and duodenum, but there were no findings of autoimmune pancreatitis. Although a small metastasis was detected in one parapancreatic lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma cells infiltrated the cancerous areas of the pancreas, but only a few IgG4-positive plasma cells were detected in the noncancerous areas.Pancreatic cancer cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive plasma cells was detected in the swollen regional lymph nodes and in the duodenal mucosa. We believe that the serum IgG4 level was elevated in this patient with pancreatic cancer as the result of an IgG4-related systemic disease that had no clinical manifestations other than lymphadenopathy.

  16. Targeting cancer-related inflammation: Chinese herbal medicine inhibits epithelial-to-mesenchymal transition in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Juan Zhang

    Full Text Available Pancreatic cancer is an almost universally fatal disease resulting from early invasion of adjacent structures and metastasis and the lack of an effective treatment modality. Our previous studies have shown that Qingyihuaji Formula (QYHJ, a seven-herb Chinese medicine formula, had significant anti-cancer effects in pancreatic cancer. Here, we examined the effects of QYHJ on pancreatic cancer cell invasion and metastasis and the potential associated mechanism(s. We found that QYHJ inhibited both tumor growth and metastasis in nude mice with human pancreatic cancer cell xenografts. Further study indicated that QYHJ inhibited epithelial-to-mesenchymal transition (EMT, which is characterized by increased E-cadherin expression and decreased vimentin, N-cadherin and Slug expression. Interleukin 6 (IL-6, a pro-inflammatory cytokine produced mainly by macrophages, could promote cancer cell EMT and invasion. In contrast, treatment with QYHJ inhibited cancer-related inflammation in tumors by decreasing infiltration of tumor-associated macrophages and IL-6 production, thus preventing cell invasion and metastasis. These results suggested that the Chinese herbal medicine QYHJ could inhibit pancreatic cancer cell invasion and metastasis in part by reversing tumor-supporting inflammation.

  17. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  18. Coffee intake and risk of pancreatic cancer: an updated meta-analysis of prospective studies.

    Science.gov (United States)

    Nie, Kechao; Xing, Zhihua; Huang, Wei; Wang, Weihao; Liu, Weiping

    2016-08-01

    Inconsistent results on the relationship between coffee consumption and pancreatic cancer risk has been reported in both epidemiological studies and previous meta-analyses. This updated meta-analysis was conducted to assess the association of coffee intake with pancreatic cancer risk. We evaluated the relationship of coffee ingestion and pancreatic cancer risk by performing a meta-analysis of prospective cohort studies and made an explicit document search in the PubMed database before November 2015. We also obtained prospective cohort studies of previous meta-analyses. A random-effects model was used for pooling overall relative risk. Twenty articles of coffee ingestion and pancreatic cancer were contained in our meta-analysis. The summary relative risk (RR) of pancreatic cancer and coffee intake of the highest compared with lowest category was 0.99 (95% CI=0.81-1.21), with statistically moderate heterogeneity (I2=47.9%, P=0.008). The heterogeneity reduced to I2=38.5% after excluding one study, and the RR was 1.06 (95% CI=0.94-1.20). The relationships of coffee intake and pancreatic risk did not modified by geographic areas, sex of participants, number of cases, follow-up years, and the number of adjusted confounders. Dose-response analysis indicated that every one-cup increase in coffee consumption was associated with an 1% increase in pancreatic cancer risk. No statistically significant publication biases existed. Coffee consumption may weakly increase the risk of pancreatic cancer.

  19. Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis

    Directory of Open Access Journals (Sweden)

    Talamini G

    2005-03-01

    Full Text Available Chronic pancreatitis patients have an increased risk of developing pancreatic cancer. The cause of this increase has yet to be fully explained but smoking and inflammation may play an important role. To these, we must now add a new potential risk factor, namely duodenal acidity. Patients with chronic pancreatitis very often present pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in chronic pancreas patients with pancreatic insufficiency has a normal concentration of s-cells and, therefore, the production of secretin is preserved. Pancreatic ductal cells are largely responsible for the amount of bicarbonate and water secretion in response to secretin stimulation. When gastric acid in the duodenum is not well-balanced by alkaline pancreatic secretions, it may induce a prolonged secretin stimulus which interacts with the pancreatic ductal cells resulting in an increased rate of ductular cell activity and turnover. N-Nitroso compounds from tobacco, identified in human pancreatic juice and known to be important carcinogens, may then act on these active cells, thereby increasing the risk of cancer. Duodenal acidity is probably of particular concern in patients who have undergone a duodenum-preserving pancreatic head resection, since, in this anatomic situation, pancreatic juice transits directly via the jejunal loop, bypassing the duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejunostomy are probably less critically affected because secretions transit, at least in part, via the papilla. If the duodenal acidity hypothesis proves correct, then, in addition to stopping smoking, reduction of duodenal acid load in patients with pancreatic insufficiency may help decrease the risk of pancreatic cancer.

  20. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Rizwani, Wasia [Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007 (India); Allen, Amanda E.; Trevino, Jose G., E-mail: Jose.Trevino@surgery.ufl.edu [Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610 (United States)

    2015-09-03

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  1. Reproductive factors, exogenous hormones, and pancreatic cancer risk in the CTS.

    Science.gov (United States)

    Lee, Eunjung; Horn-Ross, Pamela L; Rull, Rudolph P; Neuhausen, Susan L; Anton-Culver, Hoda; Ursin, Giske; Henderson, Katherine D; Bernstein, Leslie

    2013-11-01

    Female steroid hormones are hypothesized to play a protective role in pancreatic cancer risk. However, results from epidemiologic studies that examined hormone-related exposures have been inconsistent. The California Teachers Study is a cohort study of female public school professionals that was established in 1995-1996. Of the 118,164 eligible study participants, 323 women were diagnosed with incident invasive pancreatic cancer through December 31, 2009. Multivariable Cox proportional hazards regression methods were used to estimate hazard ratios and 95% confidence intervals for the association of pancreatic cancer risk with reproductive factors and exogenous hormone use. Current users of estrogen-only therapy at baseline (1995-1996) had a lower risk of pancreatic cancer than did participants who had never used hormone therapy (hazard ratio = 0.59, 95% confidence interval: 0.42, 0.84). Use of estrogen-plus-progestin therapy was not associated with the risk of pancreatic cancer. A longer duration of oral contraceptive use (≥10 years of use compared with never use) was associated with an increased risk of cancer (hazard ratio = 1.72, 95% confidence interval: 1.19, 2.49). Reproductive factors, including age at menarche, parity, breastfeeding, and age at menopause, were not associated with pancreatic cancer risk. Our results suggest that increased estrogen exposure through estrogen-only therapy may reduce pancreatic cancer risk in women.

  2. Solanine Induces Mitochondria-Mediated Apoptosis in Human Pancreatic Cancer Cells

    OpenAIRE

    Hongwei Sun; Chongqing Lv; Longlong Yang; Yingxiu Wang; Qingshun Zhang; Suhui Yu; Hongru Kong; Meng Wang; Jianming Xie; Chunwu Zhang; Mengtao Zhou

    2014-01-01

    Steroid alkaloids have been suggested as potential anticancer compounds. However, the underlying mechanisms of how steroid alkaloids inhibit the tumor growth are largely unknown. Here, we reported that solanine, a substance of steroid alkaloids, has a positive effect on the inhibition of pancreatic cancer cell growth in vitro and in vivo. In pancreatic cancer cells and nu/nu nude mice model, we found that solanine inhibited cancer cells growth through caspase-3 dependent mitochondrial apoptos...

  3. Effect of Phyllanthus amarus on serum biochemical changes in azaserine induced pancreatic cancer in Wistar rats

    OpenAIRE

    Prajapati, Ankit S.; Raval, Sunant K; Suprita Sinha; Varia, Tapan N.; Mashiyava, Parimal H.

    2015-01-01

    Aim: The present study was performed to investigate the effect of Phyllanthus amarus extracts on serum biochemical changes in azaserine induced pancreatic cancer in Wistar rats. Materials and Methods: Pancreatic cancer was developed in Wistar rats by intraperitoneal administration of azaserine (cancer inducer) for 21 days at the concentration of 5 mg/kg body weight. Aqueous and alcoholic extracts were given to rats of different groups as per protocol. Results: The results data revealed that o...

  4. Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk

    NARCIS (Netherlands)

    Jeurnink, S.M.; Ros, M.M.; Leenders, M.; Duijnhoven, F.J. van; Siersema, P.D.; Jansen, E.H.; Gils, C.H. van; Bakker, M.F.; Overvad, K.; Roswall, N.; Tjonneland, A.; Boutron-Ruault, M.C.; Racine, A.; Cadeau, C.; Grote, V.; Kaaks, R.; Aleksandrova, K.; Boeing, H.; Trichopoulou, A.; Benetou, V.; Valanou, E.; Palli, D.; Krogh, V.; Vineis, P.; Tumino, R.; Mattiello, A.; Weiderpass, E.; Skeie, G.; Castano, J.M.; Duell, E.J.; Barricarte, A.; Molina-Montes, E.; Arguelles, M.; Dorronsoro, M.; Johansen, D.; Lindkvist, B.; Sund, M.; Crowe, F.L.; Khaw, K.T.; Jenab, M.; Fedirko, V.; Riboli, E.; Bueno-de-Mesquita, H.B.

    2015-01-01

    Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-

  5. Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: A nested case-control study : Plasma micronutrients and pancreatic cancer risk

    NARCIS (Netherlands)

    Jeurnink, S.M.; Ros, M.M.; Leenders, M.; Duijnhoven, van F.J.B.

    2015-01-01

    Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case–

  6. The MUC gene family: Their role in diagnosis and early detection of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Löhr Matthias

    2003-01-01

    Full Text Available Abstract The early diagnosis of pancreatic cancer, as well as distinguishing between chronic pancreatitis and malignant pancreatic disease, remains still a clinical problem. Presently, there is no specific tumor marker for diagnosing pancreatic cancer. Mucin-associated marker like CA 19-9 are the most widely available pancreatic cancer tumor marker, but its value as a screening marker is limited by its reduced specificity. Mucins (MUCs are heavily glycosylated, high molecular weight glycoproteins with an aberrant expression profile in various malignancies. This review considers briefly the potential use of the mucin expression pattern in diagnosis of pancreatic neoplasm. The overview will point out the present knowledge about changes in the mucin gene expression in pancreatic intraepithelial neoplasia (PanINs as precursor lesions and in pancreatic adenocarcinoma, compared to normal pancreas and chronic pancreatitis and the potential role for differentiating chronic pancreatitis from pancreatic cancer. Furthermore, the potential use of MUCs in the diagnosis and differentiation of intraductal papillary-mucinous neoplasm's (IPMNs will be discussed.

  7. Effects of insulin on human pancreatic cancer progression modeled in vitro.

    Science.gov (United States)

    Chan, Michelle T; Lim, Gareth E; Skovsø, Søs; Yang, Yu Hsuan Carol; Albrecht, Tobias; Alejandro, Emilyn U; Hoesli, Corinne A; Piret, James M; Warnock, Garth L; Johnson, James D

    2014-11-06

    Pancreatic adenocarcinoma is one of the most lethal cancers, yet it remains understudied and poorly understood. Hyperinsulinemia has been reported to be a risk factor of pancreatic cancer, and the rapid rise of hyperinsulinemia associated with obesity and type 2 diabetes foreshadows a rise in cancer incidence. However, the actions of insulin at the various stages of pancreatic cancer progression remain poorly defined. Here, we examined the effects of a range of insulin doses on signalling, proliferation and survival in three human cell models meant to represent three stages in pancreatic cancer progression: primary pancreatic duct cells, the HPDE immortalized pancreatic ductal cell line, and the PANC1 metastatic pancreatic cancer cell line. Cells were treated with a range of insulin doses, and their proliferation/viability were tracked via live cell imaging and XTT assays. Signal transduction was assessed through the AKT and ERK signalling pathways via immunoblotting. Inhibitors of AKT and ERK signalling were used to determine the relative contribution of these pathways to the survival of each cell model. While all three cell types responded to insulin, as indicated by phosphorylation of AKT and ERK, we found that there were stark differences in insulin-dependent proliferation, cell viability and cell survival among the cell types. High concentrations of insulin increased PANC1 and HPDE cell number, but did not alter primary duct cell proliferation in vitro. Cell survival was enhanced by insulin in both primary duct cells and HPDE cells. Moreover, we found that primary cells were more dependent on AKT signalling, while HPDE cells and PANC1 cells were more dependent on RAF/ERK signalling. Our data suggest that excessive insulin signalling may contribute to proliferation and survival in human immortalized pancreatic ductal cells and metastatic pancreatic cancer cells, but not in normal adult human pancreatic ductal cells. These data suggest that signalling pathways

  8. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Laurila, Eeva; Vuorinen, Elisa [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Fimlab Laboratories, Biokatu 4, 33520 Tampere (Finland); Savinainen, Kimmo; Rauhala, Hanna [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Kallioniemi, Anne, E-mail: anne.kallioniemi@uta.fi [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Fimlab Laboratories, Biokatu 4, 33520 Tampere (Finland)

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.

  9. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials.

  10. Osteoprotegerin is up-regulated in pancreatic cancers and correlates with cancer-associated new-onset diabetes.

    Science.gov (United States)

    Shi, Wanchun; Qiu, Wei; Wang, Wenhua; Zhou, Xiaohui; Zhong, Xiaojing; Tian, Gang; Deng, Anmei

    2014-12-01

    New-onset diabetes might help to yield biomarkers for the early diagnosis of pancreatic cancer (PaC). In this study, we computationally predicted and experimentally validated osteoprotegerin (OPG) being associated with pancreatic cancer related new-onset diabetes. We first performed a meta-analysis on microarray datasets to search for genes specifically highly expressed in PaC, and then filtered for cytokines involved in islet dysfunction. The expression of OPG in PaC and normal pancreas were validated by immunohistochemistry. Serum OPG levels in healthy controls, non-cancerous diabetes and PaC patients with or without diabetes were detected by enzyme-linked immunosorbent assay (ELISA). In silico assay found that OPG up-regulated in PaC tissues in comparison to normal pancreas. Immunohistochemical data further confirmed that OPG was overexpressed in PaC samples. Furthermore, increased expression of OPG in PaC tissues correlated to the occurrence of new-onset diabetes, and adversely affected the patients' overall survival in both univariate and multivariate analysis. In addition, the serum levels of OPG were significantly higher in pancreatic cancer patients with new-onset diabetes than other groups including pancreatic patients without diabetes, new-onset type 2 diabetes and healthy controls. In conclusion, there is a close association between OPG and pancreatic cancer related new-onset diabetes, and OPG might serve as a potential biomarker for the early diagnosis of pancreatic cancer from populations with new-onset diabetes.

  11. Diffusion-weighted imaging of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Riccardo; De; Robertis; Paolo; Tinazzi; Martini; Emanuele; Demozzi; Flavia; Dal; Corso; Claudio; Bassi; Paolo; Pederzoli; Mirko; D’Onofrio

    2015-01-01

    Magnetic resonance imaging(MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma(PDAC). Diffusion-weighted imaging(DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues(the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion(IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation(perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.

  12. Synthesis and evaluation of cholecystokinin trimers: a multivalent approach to pancreatic cancer detection and treatment.

    Science.gov (United States)

    Brabez, Nabila; Nguyen, Kevin L; Saunders, Kara; Lacy, Ryan; Xu, Liping; Gillies, Robert J; Lynch, Ronald M; Chassaing, Gerard; Lavielle, Solange; Hruby, Victor J

    2013-04-15

    In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.

  13. Occurrence of pancreatic, biliary tract, and gallbladder cancers in Alaska Native people, 1973–2007

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    Steven R. Alberts

    2012-03-01

    Full Text Available Objectives: To describe the occurrence of pancreatic, biliary tract, and gallbladder cancers within the Alaska Native (AN population. Study design: Population-based analysis utilizing a tumor registry and comparative population data. Methods: Pancreaticobiliary cancers rates for AN people during 1973–2007 were determined from the Surveillance, Epidemiology, and End Results (SEER AN Tumor Registry. Cancer incidence rates were age-adjusted to the World Standard Million and compared over 2 time periods with US white and black rates. Results: During 1973–2007, 213 AN people developed pancreatic cancer, 73 gallbladder cancer and 61 biliary tract cancer. Pancreatic cancer occurs at similar rates in AN men and women, but data for 1993–2007 indicate that the rates among AN men may be increasing. The incidence rate in AN women (9.5/100,000 was statistically higher than in US white women (5.8/100,000. The incidence for biliary tract cancer in AN men and gallbladder cancer in AN men and women is statistically higher than that for US whites and blacks. Conclusions: Pancreaticobiliary cancers, particularly biliary tract and gallbladder cancers, in both AN men and women and pancreatic cancer in women occur at an increased rate in AN people. Risk factors relating to the elevated rate are discussed. Certain factors are potentially modifiable, such as the use of tobacco and obesity.

  14. New challenges in perioperative management of pancreatic cancer.

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    Puleo, Francesco; Maréchal, Raphaël; Demetter, Pieter; Bali, Maria-Antonietta; Calomme, Annabelle; Closset, Jean; Bachet, Jean-Baptiste; Deviere, Jacques; Van Laethem, Jean-Luc

    2015-02-28

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the industrialized world. Despite progress in the understanding of the molecular and genetic basis of this disease, the 5-year survival rate has remained low and usually does not exceed 5%. Only 20%-25% of patients present with potentially resectable disease and surgery represents the only chance for a cure. After decades of gemcitabine hegemony and limited therapeutic options, more active chemotherapies are emerging in advanced PDAC, like 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin and nab-paclitaxel plus gemcitabine, that have profoundly impacted therapeutic possibilities. PDAC is considered a systemic disease because of the high rate of relapse after curative surgery in patients with resectable disease at diagnosis. Neoadjuvant strategies in resectable, borderline resectable, or locally advanced pancreatic cancer may improve outcomes. Incorporation of tissue biomarker testing and imaging techniques into preoperative strategies should allow clinicians to identify patients who may ultimately achieve curative benefit from surgery. This review summarizes current knowledge of adjuvant and neoadjuvant treatment for PDAC and discusses the rationale for moving from adjuvant to preoperative and perioperative therapeutic strategies in the current era of more active chemotherapies and personalized medicine. We also discuss the integration of good specimen collection, tissue biomarkers, and imaging tools into newly designed preoperative and perioperative strategies.

  15. The Landscape of Pancreatic Cancer Therapeutic Resistance Mechanisms.

    Science.gov (United States)

    Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F; Winter, Jordan M; Brody, Jonathan R

    2016-01-01

    Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.

  16. Results of diagnosis of pancreatic cancer by computed tomography (CT)

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    Kimura, K.; Okuaki, K.; Ito, M.; Katakura, T.; Suzuki, K. (Fukushima Medical Coll. (Japan))

    1981-08-01

    Results of examination of pancreatic diseases, especially pancreatic cancer, conducted by CT during the past 3 years are summarized. The EMI CT Type 5000 or 5005 were used. During the 3 years from September 1976 to August 1979, a total of 1961 patients were examined by CT, and the upper abdomen was examined in 772 of these patients. In 97 patients, positive findings were obtained in the CT image of the pancreas. In 52 of these patients, the findings were confirmed operatively or by autopsy. Though cancer of the pancreas was diagnosed by CT in 30 patients, it was confirmed in 20 by surgical operation and in 1 by autopsy. Of the 9 misdiagnosed cases, 4 were cases of infiltration of the pancreas by carcinoma of the stomach or bile duct, and the other 5 were one case each of lipoma of the abdominal wall, normal pancreas, hyperplasia of Langerhans's islets of the pancreas tail, abscess between the pancreas and the posterior wall of the stomach, and choledocholithiasis. A case diagnosed by CT as cholelithiasis was a carcinoma measuring 5 x 5 x 6 cm located on the head of the pancreas, complicated by choledocholithiasis. The 22 patients with carcinoma of the pancreas were 9 with lesions less than 3.5 x 3.0 x 3.0 cm in size who could be radically operated, 6 who underwent exploratory laparotomy or autopsy, and 7 in whom operation was impossible. False negative and false positive CT results are also discussed.

  17. Intraoperative radiotherapy (IORT) for unresectable stage IVb pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, Hiroyuki; Sugimasa, Yukio; Yamada, Roppei; Akaike, Makoto; Takemiya, Shouji; Masaki, Takahiro; Miyagawa, Kaoru; Okawa, Shinichi [Kanagawa Cancer Center (Japan)

    2002-11-01

    We evaluated the efficacy of intraoperative radiotherapy (IORT) for unresectable Stage IVb (Japan Pancreas Society classification) pancreatic cancer. Twelve patients were treated with IORT, 17 with external beam radiotherapy (ERT) and 17 with chemotherapy (CHT, 8 patients doxorubicin-based, 7 patients 5-fluorouracil (5-FU)-based). Survival, hospital-free survival and pain relief were compared among the three groups. In the IORT group, 7 patients underwent bypass surgery, 3 celiac plexus blockade, 3 ERT, 2 hyperthermia and 2 CHT. In the ERT group, 1 patient underwent bypass surgery, 7 hyperthermia and 14 CHT. Distant metastases were more frequently found in the CHT group than in the IORT group. Median survival and median hospital-free survival were 208 and 79 days in the IORT group, 125 and 32 days in the ERT group and 76 and 9 days in the CHT group, respectively. Pain relief was obtained in 45% (5/11) of symptomatic patients after IORT and in 27% (4/15) after ERT. No patient (0/13) in the CHT group experienced pain relief. In conclusion, our experience suggests that IORT can reduce pain and improve quality of life (QOL) in patients with unresectable pancreatic cancer. (author)

  18. Serum Monocyte Chemoattractant Protein-1 in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer Sullivan

    2011-01-01

    Full Text Available Background/Aims. Pancreatic ductal adenocarcinoma (PDA has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n=62 and intraductal papillary mucinous neoplasms (IPMN (n=27. Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P<0.05 elevated in patients with BMI ≥ 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility.

  19. Environmental risk factors for pancreatic cancer: an update.

    Science.gov (United States)

    Barone, Elisa; Corrado, Alda; Gemignani, Federica; Landi, Stefano

    2016-11-01

    Pancreatic cancer (PC) is one of the most aggressive diseases. Only 10 % of all PC cases are thought to be due to genetic factors. Here, we analyzed the most recently published case-control association studies, meta-analyses, and cohort studies with the aim to summarize the main environmental factors that could have a role in PC. Among the most dangerous agents involved in the initiation phase, there are the inhalation of cigarette smoke, and the exposure to mutagenic nitrosamines, organ-chlorinated compounds, heavy metals, and ionizing radiations. Moreover, pancreatitis, high doses of alcohol drinking, the body microbial infections, obesity, diabetes, gallstones and/or cholecystectomy, and the accumulation of asbestos fibers seem to play a crucial role in the progression of the disease. However, some of these agents act both as initiators and promoters in pancreatic acinar cells. Protective agents include dietary flavonoids, marine omega-3, vitamin D, fruit, vegetables, and the habit of regular physical activity. The identification of the factors involved in PC initiation and progression could be of help in establishing novel therapeutic approaches by targeting the molecular signaling pathways responsive to these stimuli. Moreover, the identification of these factors could facilitate the development of strategies for an early diagnosis or measures of risk reduction for high-risk people.

  20. Factors influencing receptivity to future screening options for pancreatic cancer in those with and without pancreatic cancer family history

    Directory of Open Access Journals (Sweden)

    Breitkopf Carmen

    2012-06-01

    Full Text Available Abstract Background Pancreatic cancer (PC is considered the most lethal cancer and approximately 10% of PC is hereditary. The purpose of the study was to assess attitudes of at-risk family members with two or more relatives affected with pancreas cancer (PC toward PC risk and future screening options. Methods At-risk family members and primary care controls were surveyed regarding perceived PC risk, PC worry/concern, attitude toward cancer screening, screening test accuracy, and intentions regarding PC screening via blood testing or more invasive endoscopic ultrasound (EUS. Results PC family members reported greater perceived risk of PC than controls (54% vs. 6%, respectively, p 89% receptivity to the potential PC screening options presented, though receptivity was greater among PC family members as compared to controls (p  Conclusions Receptivity to screening options for PC appears high. Clinicians should address behavioral and genetic risk factors for PC and foster appropriate concern regarding PC risk among at-risk individuals.

  1. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

    Science.gov (United States)

    Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

    2012-01-01

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10−6, 1.6 × 10−5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10−5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

  2. Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

    Science.gov (United States)

    Feng, Hui-Yi; Chen, Yang-Chao

    2016-09-07

    The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis.

  3. Dietary glycemic index and glycemic load and risk of pancreatic cancer: a case-control study.

    Science.gov (United States)

    Rossi, Marta; Lipworth, Loren; Polesel, Jerry; Negri, Eva; Bosetti, Cristina; Talamini, Renato; McLaughlin, Joseph K; La Vecchia, Carlo

    2010-06-01

    Carbohydrates and dietary glycemic index (GI) influence the secretion of insulin and insulin-related growth factors and may play a role in the development of diabetes and obesity, both of which have been related to pancreatic cancer risk. We examined the association between dietary GI and glycemic load (GL) and pancreatic cancer by conducting a hospital-based case-control study in Italy in 1991-2008 of 326 cases of pancreatic cancer and 652 control patients. Dietary data were obtained with the use of a validated food-frequency questionnaire. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were computed with the use of multiple logistic regression. GI was positively associated with pancreatic cancer, with ORs of 1.56 (95% CI, 1.06-2.30) and 1.78 (95% CI, 1.20-2.62) for the second and third tertiles, respectively, compared with the lowest. No significant association was observed between GL and pancreatic cancer. Consumption of sugar, candy, honey, and jam was positively associated with pancreatic cancer, whereas consumption of fruit was inversely associated. In conclusion, the positive association with high GI, in the absence of an association with dietary GL, fruit, or total carbohydrates, likely reflects the positive association between sweets or refined carbohydrates and pancreatic cancer in this study population. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Serum Protein Fingerprint of Patients with Pancreatic Cancer by SELDI Technology

    Institute of Scientific and Technical Information of China (English)</