Cannabinoids as Adjunct Treatment for Pancreatic Cancer

Published by Jan

 

Pancreatic Cancer-


What is pancreatic cancer?
Cancers that develop within the pancreas fall into two major categories: (1) cancers of the endocrine pancreas (the part that makes insulin) are called "islet cell" or "pancreatic neuroendocrine" cancers and (2) cancers of the exocrine pancreas (the part that makes enzymes).  Islet cell cancers are rare and typically grow slowly compared to exocrine pancreatic cancers.  Islet cell tumors often release hormones into the bloodstream and are further characterized by the hormones they produce (insulin, glucagon, gastrin, and other hormones).  Cancers of the exocrine pancreas develop from the cells that line the system of ducts that deliver enzymes to the small intestine and are called pancreatic adenocarcinomas.  Adenocarcinoma of the pancreas comprises ninety five percent  of all pancreatic ductal cancers and is the subject of this review.
Cells that line the ducts in the exocrine pancreas divide more rapidly than the tissues that surround them. For reasons that we do not understand, these cells can make a mistake when they divide and an abnormal cell can be made.  When an abnormal ductal cell begins to divide in an unregulated way, a growth can form. These changes are called "dysplasia."  Often, dysplastic cells can undergo additional genetic mistakes over time and become even more abnormal.  If these dysplastic cells then begin to invade through the walls of the duct from which they arise into the surrounding tissue, a cancer develops.


Pancreatic carcinoma is cancer of the pancreas.


The pancreas is a large organ that is found behind the stomach.  It makes and releases enzymes that help the body breakdown proteins  (especially fats).  It also makes the hormone insulin  (and glucagon)  that regulate blood sugar levels.  
The exact cause is unknown, but pancreatic cancer is more common in smokers and people who are obese. Pancreatic cancer is slightly more common in women than in men.  The risk increases with age.  A small number of cases are related to genetic syndromes that are passed down through families.


Symptoms


A tumor or cancer in the pancreas may often grow without any symptoms at first.  This may mean pancreatic cancer is more advanced when it is first found.
o Early symptoms of pancreatic cancer include:
o Pain or discomfort in the upper part of the belly or abdomen
o Loss of appetite and weight loss
o Jaundice (a yellow color in the skin, mucus membranes, or the eyes)
o Dark urine and clay-colored stools
o Fatigue and weakness
o Nausea and vomiting

Other possible symptoms are:
• Back pain
• Blood clots
• Depression
• Diarrhea
• Difficulty sleeping
• Indigestion


Presentation


Pancreatic cancer is sometimes called a "silent killer" because early pancreatic cancer often does not cause symptoms,  and the later symptoms are usually nonspecific and varied.  Therefore, pancreatic cancer is often not diagnosed until it is advanced. 
Most patients with pancreatic cancer experience pain, weight loss, or jaundice.
Pain is present in 80% to 85% of patients with locally advanced or advanced metastatic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back.  It may be intermittent and made worse by eating.  Weight loss can be profound;  it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine.  Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.
The initial presentation varies according to location of the cancer.  Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice.  The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted.  Courvoisier sign defines the presence of jaundice and a painlessly distendedgallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones. Tiredness, irritability and difficulty eating because of pain also exist.  Pancreatic cancer is often discovered during the course of the evaluation of aforementioned symptoms.


Pancreatic cancer facts

 


1. Most pancreatic cancers are adenocarcinomas

2. Few patients diagnosed with pancreatic cancer have identifiable risk factors.

3. Pancreatic cancer is highly lethal.

4. Pancreatic cancer is difficult to diagnose, and the diagnosis is often made late in the disease course. Symptoms include weight loss, back pain, and jaundice.

5. The only curable treatment is surgical removal of all of the cancer.

6. Chemotherapy after surgery can lower the chances of the cancer returning.

7. Chemotherapy for metastatic pancreatic cancer can extend life and improve the quality of life for people with the disease.

8. Patients diagnosed with pancreatic cancer are encouraged to seek out clinical trials to improve pancreatic cancer treatment.

 

Pancreatic cancer refers to a malignant neoplasm of the pancreas.  The most common type of pancreatic cancer, accounting for ninety five percent  of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas.  A minority arises from the islet cells and is classified as a neuroendocrine tumor.  The symptoms that lead to diagnosis depend on the location, the size, and the tissue type of the tumor. 
Pancreatic cancer is the fourth most common cause of cancer death both in the United States  and internationally.    Pancreatic cancer often has a poor prognosis:   for all stages combined, the (one and five year)  relative survival rates are twenty five percent  and six percent respectively,  while the median survival for locally advanced and for metastatic disease,  which collectively represent over eighty percent  of individuals,  is about ten  and six months respectively.


Expectations (prognosis)


Some patients with pancreatic cancer that can be surgically removed are cured.  However, in more than eighty percent of patients the tumor has already spread and cannot be completely removed at the time of diagnosis.
Chemotherapy and radiation are often given after surgery to increase the cure rate (this is called adjuvant therapy).  For pancreatic cancer that cannot be removed completely with surgery, or cancer that has spread beyond the pancreas, a cure is not possible and the average survival is usually less than one  year. Such patients should consider enrolling in a clinical trial (a medical research study to determine the best treatment).  Five to ten percent of pancreatic cancer patients have a family history of pancreatic cancer.


"Ninety-five percent of the people diagnosed with this cancer will not be alive in five  years"

.

Complications


• Blood clots
• Depression
• Infections
• Liver problems
• Pain
• Weight loss


Calling your health care provider
Call for an appointment with your health care provider if you have:
• Back pain
• Unexplained fatigue or weight loss
• Loss of appetite
• Persistent abdominal pain
• Other symptoms of this disorder


Prevention


• If you smoke, stop smoking.
• Eat a diet high in fruits, vegetables, and whole grains.
• Exercise regularly.

 

Surgery


Treatment of pancreatic cancer depends on the stage of the cancer.  The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas.  This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gastro-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy).  It can be performed only if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing.  It can, therefore, be performed in only the minority of cases.
Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.  Recently,  localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches.
After surgery, adjuvant chemotherapy with gemcitabine has been shown in several large randomized studies to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery
Surgery can be performed for palliation, if the malignancy is invading or compressing the duodenum or colon.  In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure.


Chemotherapy
In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998, after a clinical trial reported improvements in quality of life and a 5-week improvement in median survival duration in patients with advanced pancreatic cancer.  This marked the first FDA approval of a chemotherapy drug primarily for a nonsurvival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis.


Prognosis


Exocrine pancreatic cancer (adenocarcinoma and less common variants) typically has a poor prognosis, partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis.
Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered, and it has been suggested the cancer can also prompt the onset of diabetes and vice versa.[65] It can be associated with pain, fatigue, weight loss, jaundice, and weakness. Additional symptoms are discussed above.
For pancreatic cancer:
? For all stages combined, the 1-year relative survival rate is 25%, and the 5-year survival is estimated as less than five to six percent. 

 ? For local disease, the 5-year survival is approximately 20%.
? For locally advanced and for metastatic disease, which collectively represent over 80% to 85-90%of individuals, the median survival is about 10 and 6 months, respectively. Without active treatment, metastatic pancreatic cancer has a median survival of 3–5 months; complete remission is rare.
?  Outcomes with pancreatic endocrine tumors, many of which are benign and completely without clinical symptoms, are much better, as are outcomes with symptomatic benign tumors; even with actual pancreatic endocrine cancers, outcomes are rather better, but variable.


In 2010, an estimated 43,000 people in the US were diagnosed with pancreas cancer and almost 37,000 died from the disease; pancreatic cancer has one of the highest fatality rates of all cancers, and is the fourth-highest cancer killer in the US and internationally among both men and women.  Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for six percent  of cancer deaths each year.


 
Cannabinoids as Adjunct Treatment for Pancreatic Cancer


Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes" and "Delta-9-tetrahydrocannabinol inhibits cell cycle progression in pancreatic cells.

Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of special interest to set new strategies aimed at improving the prognostic of this deadly disease.  The present study was undertaken to investigate the action of cannabinoids,  a new family of potential antitumoral agents,  in pancreatic cancer cells.Despite many years of intensive research, pancreatic cancer remains as the fourth leading cause of cancer death in the United States and the fifth in the Western world overall .  Current approved therapies based on the administration of fluorouracil chemoradiation for locally advanced tumors and gemcitabine chemotherapy for metastatic disease have only slightly increased the median survival of affected patients .  In the present report, we show that cannabinoids induce apoptosis of pancreatic tumor cell lines in vitro and exert a remarkable growth-inhibiting effect in models of pancreatic cancer in vivo.
Although the pancreatic tumor biopsies and cell lines analyzed expressed both CB1 and CB2 cannabinoid receptors, our findings indicate that the CB2 receptor is the one that plays a major role in the proapoptotic effect of cannabinoids in these cells.
In conclusion, results presented here show that cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells.  Cannabinoid treatment increases TRB3 expression and apoptosis in pancreatic tumors but not in normal pancreatic tissue. Intrapancreatic tumors were generated as described in Materials and Methods. Animals were treated with either vehicle or WIN 55,212-2 (1.5 mg/kg for 2 days, 2.25 mg/kg for 2 additional days, and 3.0 mg/kg for 10 additional days; n = 6 for each experimental group).  The day after the 14-day treatment, animals were sacrificed, pancreatic tissues containing tumors were fixed, and sections were prepared.   A, representative images ( 40) of TUNEL-stained pancreatic tumors.  Values in the lower left corner of the bottom images correspond to 12 sections of three dissected tumors for each condition and are expressed as the percentage of TUNEL-positive cells relative to the total number of cells in each section. B, representative images ( 20) of TUNEL-stained pancreas.  T, tumor tissue; P, normal pancreatic tissue.  C, representative images ( 40) of TRB3-stained pancreatic tumors. Values in the lower left corner of the bottom images correspond to 18 sections of three dissected tumors for each condition and are expressed as the percentage of TRB3-stained area relative to the total area in each section. D, schematic representation of the proposed mechanism of cannabinoid-induced apoptosis on pancreatic tumor cells.
Cancer Research:  in vitro and in vivo due to their ability to selectively induce apoptosis of these cells via activation of the p8-ATF-4-TRB3 proapoptotic pathway.  These findings may help to set the basis for a new therapeutic approach for the treatment of this deadly disease.



In recent years, there has been increasing interest in cannabinoids as therapeutic drugs for their antineoplastic, anticachectic, and analgesic potential.  Growth inhibitory activities of cannabinoids have been demonstrated for various malignancies,  including brain,  breast,  prostate,  colorectal,  skin and, recently,  pancreatic cancer.
Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of < 20%.  The purpose of our work was to improve GEM activity by addition of cannabinoids.  Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments.   In recent years, there has been increasing interest in cannabinoids as therapeutic drugs for their antineoplastic, anticachectic, and analgesic potential.   Growth inhibitory activities of cannabinoids have been demonstrated for various malignancies, including brain, breast, prostate, colorectal, skin and, recently, pancreatic cancer.

Madrid, Spain: Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.
These findings may contribute to ... a new therapeutic approach for the treatment of pancreatic cancer," authors concluded.

Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells.
In conclusion, we show that the endocannabinoid system is down regulated in chronic pancreatitis and that administered cannabinoids specifically reduces activation of pancreatic stellate cells.  And suppresses pro-inflammatory cytokines.

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say

Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, "cannabinoid treatment inhibited the spreading of pancreatic tumor cells ... and reduced the growth of tumor cells" in animals.
Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes"


 

Recommendation:
Cannabinoids  make an excellent choice for the adjunct treatment of pancreatic cancer.
Indica x Sativa hybrid (Indica dominant)  (high CBD/THC levels)
Whole plant extracts taken under the tongue 2-4 times daily.

 

                           

 

                                                                                                                                                            pancreatic cancer

 

 

References:__________________________________________________________________________________________________________________________________________________________________________________
Tempero M, Brand R. Pancreatic cancer. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 204.
^ a b c d e f g h American Cancer Society: Cancer Facts & Figures 2010: see page 4 for incidence estimates, and page 19 for survival percentageshttp://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf
^ a b Hariharan, D.; Saied, A.; Kocher, H. M. (2008). "Analysis of mortality rates for pancreatic cancer across the world". HPB 10 (1): 58–62. doi:10.1080/13651820701883148. PMC 2504856.PMID 18695761. edit
^ a b c d National Cancer Institute. General Information About Pancreatic Cancer.http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional
^ a b c d Benson AB, Myerson RJ, and Sasson AR. Pancreatic, Neuroendocrine GI, and Adrenal Cancers. Cancer Management 13th edition. http://www.cancernetwork.com/cancer-management/pancreatic/article/10165/1802606
^ a b c d e f g "What You Need To Know About Cancer of the Pancreas — National Cancer Institute". 2002-09-16. p. 4/5. Retrieved 2007-12-22.
^ Pannala R, Basu A, Petersen GM, Chari ST (January 2009). "New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer". The Lancet Oncology 10 (1): 88–95. doi:10.1016/S1470-2045(08)70337-1. PMC 2795483. PMID 19111249.
^ Carney CP, Jones L, Woolson RF, Noyes R, Doebbeling BN (2003). "Relationship between depression and pancreatic cancer in the general population". Psychosomatic Medicine 65 (5): 884–8.doi:10.1097/01.PSY.0000088588.23348.D5. PMID 14508036.
^ Medscape > Pancreatic Cancer Author: Tomislav Dragovich. Chief Editor: Jules E Harris. Updated: May 5, 2011
^ AJCC Cancer Staging Manual 2nd edition; Chapter 15; Pancreas - original pages 95-98; page 95 for citation regarding "...lesser degree of involvement of bones and brain and other anatomical sites."http://www.cancerstaging.org/products/csmanual2ed.pdf
^ "ACS :: What Are the Risk Factors for Cancer of the Pancreas?". Archived from theoriginal on October 12, 2007. Retrieved 2007-12-13.
^ a b c d e Ghaneh P, Costello E, Neoptolemos JP (August 2007). "Biology and management of pancreatic cancer". Gut 56 (8): 1134–52.doi:10.1136/gut.2006.103333. PMC 1955499. PMID 17625148.
^ Efthimiou E, Crnogorac-Jurcevic T, Lemoine NR, Brentnall TA (February 2001). "Inherited predisposition to pancreatic cancer". Gut48 (2): 143–7. doi:10.1136/gut.48.2.143. PMC 1728218.PMID 11156628.
^ Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (July 2008). "Tobacco and the risk of pancreatic cancer: a review and meta-analysis". Langenbeck's Archives of Surgery 393 (4): 535–45.doi:10.1007/s00423-007-0266-2. PMID 18193270.
^ a b Chan JM, Wang F, Holly EA (September 2005). "Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area". Cancer Epidemiology, Biomarkers & Prevention 14 (9): 2093–7. doi:10.1158/1055-9965.EPI-05-0226. PMID 16172215.
^ "Red Meat May Be Linked to Pancreatic Cancer". Journal of the National Cancer Institute. WebMD. 2005-10-05. Retrieved 2008-03-05.
^ "Soft Drink and Juice Consumption and Risk of Pancreatic Cancer: The Singapore Chinese Health Study".
^ "Cancer cells slurp up fructose, U.S. study says". Reuters. 2010-08-02. Retrieved 2010-08-02.
^ "Obesity Linked to Pancreatic Cancer". American Cancer Society. Cancer Epidemiology, Biomarkers & Prevention (Vol. 14, No. 2: 459–466). 2005-03-06. Archived from the original on February 5, 2008. Retrieved 2008-03-05.
^ Raderer, M.; Wrba, F.; Kornek, G.; Maca, T.; Koller, D.Y.; Weinlaender, G.; Hejna, M.; Scheithauer, W. (1998). "Association between Helicobacter pylori Infection and Pancreatic Cancer".Oncology 55 (1): 16–19. doi:10.1159/000011830. PMID 9428370.edit
^ Stolzenberg-Solomon, R. Z.; Blaser, M. J.; Limburg, P. J.; Perez-Perez, G.; Taylor, P. R.; Virtamo, J.; Albanes, D. (2001). "Helicobacter pylori Seropositivity as a Risk Factor for Pancreatic Cancer". JNCI Journal of the National Cancer Institute 93 (12): 937–941.doi:10.1093/jnci/93.12.937. edit
^ Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (January 2007). "A prospective study of periodontal disease and pancreatic cancer in US male health professionals". Journal of the National Cancer Institute 99 (2): 171–5. doi:10.1093/jnci/djk021. PMID 17228001.
^ National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
^ American Cancer SocietyCoffee and Alcohol Do Not Pose a Risk for Pancreatic Cancer
^ Villeneuve PJ, Johnson KC, Hanley AJ, Mao Y (February 2000). "Alcohol, tobacco and coffee consumption and the risk of pancreatic cancer: results from the Canadian Enhanced Surveillance System case-control project. Canadian Cancer Registries Epidemiology Research Group". European Journal of Cancer Prevention 9 (1): 49–58. doi:10.1097/00008469-200002000-00007. PMID 10777010.
^ a b Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (May 2001). "Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts".Cancer Epidemiology, Biomarkers & Prevention 10 (5): 429–37.PMID 11352851.
^ Cancer Research UK Pancreatic cancer risks and causes
^ Ahlgren JD (April 1996). "Epidemiology and risk factors in pancreatic cancer". Seminars in Oncology 23 (2): 241–50. PMID 8623060.
^ Cuzick J, Babiker AG (March 1989). "Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease". International Journal of Cancer 43 (3): 415–21. doi:10.1002/ijc.2910430312.PMID 2925272.
^ Harnack LJ, Anderson KE, Zheng W, Folsom AR, Sellers TA, Kushi LH (December 1997). "Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women's Health Study". Cancer Epidemiology, Biomarkers & Prevention 6(12): 1081–6. PMID 9419407.
^ Schottenfeld, D. and J. Fraumeni, ed. Cancer epidemiology and prevention. 2nd ed., ed. Vol. 1996, Oxford University Press: Oxford[page needed]
^ a b Ye W, Lagergren J, Weiderpass E, Nyrén O, Adami HO, Ekbom A (August 2002). "Alcohol abuse and the risk of pancreatic cancer". Gut51 (2): 236–9. doi:10.1136/gut.51.2.236. PMC 1773298.PMID 12117886.
^ a b Silverman DT, Brown LM, Hoover RN, et al. (November 1995)."Alcohol and pancreatic cancer in blacks and whites in the United States". Cancer Research 55 (21): 4899–905. PMID 7585527.
^ Olsen GW, Mandel JS, Gibson RW, Wattenberg LW, Schuman LM (August 1989). "A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet". American Journal of Public Health 79 (8): 10169. doi:10.2105/AJPH.79.8.1016.PMC 1349898. PMID 2751016.
^ "Pancreatic cancer risk factors". Info.cancerresearchuk.org. 2008-11-04. Retrieved 2009-09-15.
^ a b c "In summary, a weak positive association between alcohol intake during adulthood and pancreatic cancer risk was observed in the highest category of intake (≥30g/day or approximately 2 alcoholic beverages/day). Associations with alcohol intake were stronger among individuals who were normal weight. Thus, our findings are consistent with a modest increase in risk of pancreatic cancer for alcohol intakes of at least 30 grams/day." Genkinger JM, Spiegelman D, Anderson KE, et al. (March 2009). "Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies". Cancer Epidemiology, Biomarkers & Prevention 18 (3): 765–76.doi:10.1158/1055-9965.EPI-08-0880. PMC 2715951.PMID 19258474.
^ Zatonski WA, Boyle P, Przewozniak K, Maisonneuve P, Drosik K, Walker AM (February 1993). "Cigarette smoking, alcohol, tea and coffee consumption and pancreas cancer risk: a case-control study from Opole, Poland". International Journal of Cancer 53 (4): 601–7.doi:10.1002/ijc.2910530413. PMID 8436433.
^ Durbec JP, Chevillotte G, Bidart JM, Berthezene P, Sarles H (April 1983). "Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study". British Journal of Cancer 47 (4): 463–70.PMC 2011343. PMID 6849792.
^ Bueno de Mesquita HB, Maisonneuve P, Moerman CJ, Runia S, Boyle P (February 1992). "Lifetime consumption of alcoholic beverages, tea and coffee and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands".International Journal of Cancer 50 (4): 514–22.doi:10.1002/ijc.2910500403. PMID 1537615.
^ Bakkevold KE, Arnesjø B, Kambestad B (April 1992). "Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial".Scandinavian Journal of Gastroenterology 27 (4): 317–25.doi:10.3109/00365529209000081. PMID 1589710.
^ Frank J. Domino M.D. (2007). 5 minutes clinical suite version 3. Philadelphia, PA: Lippincott Williams & Wilkins.[page needed]
^ a b Philip Agop, "Pancreatic Cancer". ACP PIER & AHFX DI Essentials. American College of Physicians. 4 Apr 2008. Accessed 7 Apr 2009.[page needed]
^ a b c Johns Hopkins Medicine; The Sol Goldman Pancreas Cancer Research Center. Types of Pancreas Tumors.http://pathology.jhu.edu/pancreas/BasicTypes1.php
^ a b c d e f g h Yao, J. C.; Eisner, M. P.; Leary, C.; Dagohoy, C.; Phan, A.; Rashid, A.; Hassan, M.; Evans, D. B. (2007). "Population-Based Study of Islet Cell Carcinoma". Annals of Surgical Oncology 14 (12): 3492–3500. doi:10.1245/s10434-007-9566-6. PMC 2077912.PMID 17896148. edit
^ "The prognosis of patients with PENs is difficult to predict, in part because the definition of malignancy in PENs has been ambiguous. By some, PENs have been defined as malignant only when lymph nodes are involved or liver metastases are documented. Other investigators have included vascular invasion or invasion of adjacent structures as evidence of malignancy. However, the concept that a PEN removed successfully without recurrence was therefore biologically benign could be challenged. In fact, strict separation of PENs into benign and malignant groups may be less clinically useful than the definition of prognostic factors."Hochwald, S. N.; Zee, S.; Conlon, K.; Colleoni, R.; Louie, O.; Brennan, M.; Klimstra, D. (2002). "Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases with a Proposal for Low-Grade and Intermediate-Grade Groups". Journal of Clinical Oncology 20 (11): 2633–2642.doi:10.1200/JCO.2002.10.030. PMID 12039924. edit
^ "One of the most controversial aspects of PENs has been the prediction of prognosis."Klimstra, D. S. (2007). "Nonductal neoplasms of the pancreas". Modern Pathology 20: S94–S112.doi:10.1038/modpathol.3800686. PMID 17486055. edit
^ "The classification of these tumors remains controversial, and prognosis is difficult to predict" Wendy L. Frankel (2006) Update on Pancreatic Endocrine Tumors. Archives of Pathology & Laboratory Medicine: July 2006, Vol. 130, No. 7, pp. 963-966.http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2006)130[963:UOPET]2.0.CO;2
^ Modlin http://onlinelibrary.wiley.com/doi/10.1002/cncr.11105/pdf
^ "Can Cancer of the Pancreas Be Prevented?". American Cancer Society. Archived from the original on October 12, 2007. Retrieved 2007-12-13.
^ Coughlin SS, Calle EE, Patel AV, Thun MJ (December 2000). "Predictors of pancreatic cancer mortality among a large cohort of United States adults". Cancer Causes & Control 11 (10): 915–23.doi:10.1023/A:1026580131793. ISSN 0957-5243.PMID 11142526.
^ Zheng W, McLaughlin JK, Gridley G, et al. (September 1993). "A cohort study of smoking, alcohol consumption, and dietary factors for pancreatic cancer (United States)". Cancer Causes & Control 4 (5): 477–82. doi:10.1007/BF00050867. PMID 8218880.
^ Larsson SC, Håkansson N, Näslund I, Bergkvist L, Wolk A (February 2006). "Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study". Cancer Epidemiology, Biomarkers & Prevention 15 (2): 301–05. doi:10.1158/1055-9965.EPI-05-0696.PMID 16492919.
^ "Health | Vitamin D 'slashes cancer risk'". BBC News. 2006-09-15. Retrieved 2009-09-15. The BBC quoted the lead researcher: "I would make no specific recommendation for vitamin D supplementation to prevent pancreatic cancer until we can carry out a trial to determine definitively who might benefit from such an intervention." The BBC quoted Henry Scowcroft, science information officer at the charity Cancer Research UK: "The results of this study don't mean that people should take vitamin D supplements to ward off pancreatic cancer, especially as vitamin D can be harmful in large quantities...As the authors themselves point out, this is the very first study to find any association between the disease and vitamin D intake...So this result needs to be repeated in other large studies, and scientists need to show exactly how vitamin D might prevent pancreatic cancer before we could issue any specific lifestyle advice."
^ "Vitamin D May Cut Pancreatic Cancer". Webmd.com. 2006-09-12.
^ a b Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx Dietary Reference Intakes for Calcium and Vitamin D IOM, November 30, 2010: "The IOM finds that the evidence supports a role for vitamin D and calcium in bone health but not in other health conditions. Further, emerging evidence indicates that too much of these nutrients may be harmful, challenging the concept that “more is better.”
^ World Health Organization; International Agency for Research on Cancer (IARC). Vitamin D and Cancer. IARC Working Group Reports Vol.5, International Agency for research on Cancer, Lyon, 25 November 2008
^ Lipson P. Vitamin D: Still more questions than answers.http://blogs.forbes.com/sciencebiz/2010/08/18/vitamin-d-still-more-questions-than-answers/ "Vitamin D deficiency is common in people with poor diets (including obese people) and in people who are relatively inactive. These are independent risk factors for... ...some cancers. And while some cellular mechanisms have been discovered that may lend plausibility to a vitamin D hypothesis, there are as of yet no convincing data that allow us to draw conclusions about vitamin D and these diseases."
^ United Press International (2 June 2007). "Pancreatic cancer risk cut by B6, B12". Retrieved 5 September 2009.
^ Schernhammer E, Wolpin B, Rifai N, et al. (June 2007). "Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts". Cancer Research 67 (11): 5553–60.doi:10.1158/0008-5472.CAN-06-4463. PMID 17545639.
^ a b "Surgical Treatment of Pancreatic Cancer". Johns Hopkins University. Retrieved 5 September 2009.
^ "Laparoscopic Pancreas Surgery". Johns Hopkins University. Retrieved 5 September 2009.
^ Neoptolemos JP, Stocken DD, Friess H, et al. (March 2004). "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer". The New England Journal of Medicine350 (12): 1200–10. doi:10.1056/NEJMoa032295.PMID 15028824.
^ "Tarceva® (erlotinib) Tablets. NDA 21-743, S003. Supplemental NDA: Pancreatic Cancer, Briefing Document, ODAC Meeting 13 September 2005". September 2005. Retrieved 2009-09-15.
^ Moore et al. JCO 2005
^ Demols A, Peeters M, Polus M, et al. (February 2006). "Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study". British Journal of Cancer 94 (4): 481–85. doi:10.1038/sj.bjc.6602966.PMC 2361170. PMID 16434988.
^ Wang F, Herrington M, Larsson J, Permert J (January 2003). "The relationship between diabetes and pancreatic cancer". Molecular Cancer 2: 4. doi:10.1186/1476-4598-2-4. PMC 149418.PMID 12556242.
^ "WHO | Cancer". Who.int. Retrieved 2009-09-15.
^ Fesinmeyer, M. D.; Austin, M. A.; Li, C. I.; De Roos, A. J.; Bowen, D. J. (2005). "Differences in Survival by Histologic Type of Pancreatic Cancer". Cancer Epidemiology Biomarkers & Prevention 14 (7): 1766–1773. doi:10.1158/1055-9965.EPI-05-0120. edit
^ "Pancreatic Cancer — National Cancer Institute, U.S. National Institutes of Health (Accessed 28 April 2011)". Cancer.gov. Retrieved 2009-09-15.
^ Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007). "Cancer statistics, 2007". CA 57 (1): 43–66. doi:10.3322/canjclin.57.1.43.PMID 17237035.
^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov. 11, 2009.
1. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer.
Lancet 2004;363:1049–57.
2. Edwards BK, Brown ML, Wingo PA, et al. Annual
report to the nation on the status of cancer, 1975–2002,
featuring population-based trends in cancer treatment.
J Natl Cancer Inst 2005;97:1407–27.
3. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E,
Thun MJ. Cancer statistics. CA Cancer J Clin 2003;53:
5–26.
4. Gaoni Y, Mechoulam R. Isolation, structure and partial
synthesis of an active constituent of hashish. J Am Chem
Soc 1964;86:1646–7.
5. Devane WA, Hanus L, Breuer A, et al. Isolation and
structure of a brain constituent that binds to the
cannabinoid receptor. Science 1992;258:1946–9.
6. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification
of an endogenous 2-monoglyceride, present in
canine gut, that binds to cannabinoid receptors.
Biochem Pharmacol 1995;50:83–90.
7. Howlett AC, Barth F, Bonner TI, et al. International
Union of Pharmacology. XXVII. Classification of cannabinoid
receptors. Pharmacol Rev 2002;54:161–202.
8. Munro S, Thomas KL, Abu-Shaar M. Molecular
characterization of a peripheral receptor for cannabinoids.
Nature 1993;365:61–5.
9. Galve-Roperh I, Sanchez C, Cortes ML, Go´mez del
Pulgar T, Izquierdo M, Guzman M. Anti-tumoral action
of cannabinoids: involvement of sustained ceramide
accumulation and extracellular signal-regulated kinase
activation. Nat Med 2000;6:313–9.
10. Benito C, Nunez E, Tolon RM, et al. Cannabinoid
CB2 receptors and fatty acid amide hydrolase are
selectively overexpressed in neuritic plaque-associated
glia in Alzheimer’s disease brains. J Neurosci 2003;23:
11136–41.
11. Casanova ML, Blazquez C, Martinez-Palacio J, et al.
Inhibition of skin tumor growth and angiogenesis
in vivo by activation of cannabinoid receptors. J Clin
Invest 2003;111:43–50.
12. Guzman M. Cannabinoids: potential anticancer
agents. Nat Rev Cancer 2003;3:745–55.
13. Blazquez C, Gonzalez-Feria L, Alvarez L, Haro A,
Casanova ML, Guzman M. Cannabinoids inhibit the
vascular endothelial growth factor pathway in gliomas.
Cancer Res 2004;64:5617–23.
14. Blazquez C, Casanova ML, Planas A, et al. Inhibition
of tumor angiogenesis by cannabinoids. FASEB J 2003;
17:529–31.
15. Portella G, Laezza C, Laccetti P, De Petrocellis L, Di
Marzo V, Bifulco M. Inhibitory effects of cannabinoid
CB1 receptor stimulation on tumor growth and
metastatic spreading: actions on signals involved in
angiogenesis and metastasis. FASEB J 2003;17:1771–3.
16. Melck D, De Petrocellis L, Orlando P, et al.
Suppression of nerve growth factor Trk receptors and
prolactin receptors by endocannabinoids leads to
inhibition of human breast and prostate cancer cell
proliferation. Endocrinology 2000;141:118–26.
17. De Petrocellis L, Melck D, Palmisano A, et al. The
endogenous cannabinoid anandamide inhibits human
breast cancer cell proliferation. Proc Natl Acad Sci U S A
1998;95:8375–80.
18. McKallip RJ, Lombard C, Fisher M, et al. Targeting
CB2 cannabinoid receptors as a novel therapy to
treat malignant lymphoblastic disease. Blood 2002;100:
627–34.
19. Sanchez C, de Ceballos ML, del Pulgar TG, et al.
Inhibition of glioma growth in vivo by selective
activation of the CB(2) cannabinoid receptor. Cancer
Res 2001;61:5784–9.
20. Gomez del Pulgar T, Velasco G, Sanchez C, Haro A,
Guzman M. De novo-synthesized ceramide is involved in
cannabinoid-induced apoptosis. Biochem J 2002;363:
183–8.
21. Hanada K. Serine palmitoyltransferase, a key enzyme
of sphingolipid metabolism. Biochim Biophys Acta 2003;
1632:16–30.
22. Encinar JA, Mallo GV, Mizyrycki C, et al. Human p8 is
a HMG-I/Y-like protein with DNA binding activity
enhanced by phosphorylation. J Biol Chem 2001;276:
2742–51.
23. Malicet C, Lesavre N, Vasseur S, Iovanna JL. p8
inhibits the growth of human pancreatic cancer cells
and its expression is induced through pathways
involved in growth inhibition and repressed by factors
promoting cell growth. Mol Cancer 2003;2:37.
24. Vasseur S, Vidal Mallo G, Fiedler F, et al.
Cloning and expression of the human p8, a nuclear
protein with mitogenic activity. Eur J Biochem 1999;
259:670–5.
25. Carracedo A, Lorente M, Egia A, et al. The stressregulated
protein p8 mediates cannabinoid-induced
apoptosis of tumor cells. Cancer Cell 2006;9:301–12.
26. Ma Y, Brewer JW, Diehl JA, Hendershot LM. Two
distinct stress signaling pathways converge upon the
CHOP promoter during the mammalian unfolded
protein response. J Mol Biol 2002;318:1351–65.
27. Back SH, Schroder M, Lee K, Zhang K, Kaufman RJ.
ER stress signaling by regulated splicing: IRE1/HAC1/
XBP1. Methods 2005;35:395–416.
28. Ord D, Ord T. Characterization of human NIPK
(TRB3, SKIP3) gene activation in stressful conditions.
Biochem Biophys Res Commun 2005;330:210–8.
29. Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H.
TRB3, a novel ER stress-inducible gene, is induced via
ATF4-CHOP pathway and is involved in cell death.
EMBO J 2005;24:1243–55.
30. Sarfaraz S, Afaq F, Adhami VM, Mukhtar H.
Cannabinoid receptor as a novel target for the
treatment of prostate cancer. Cancer Res 2005;65:
1635–41.
31. Mayumi-Matsuda K, Kojima S, Suzuki H, Sakata T

 

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