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Fulltext Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Klein AP, Wolpin BM, Risch HA, Stolzenberg-Solomon RZ, Mocci E, Zhang M, et al.

Nat Commun, 2018 02 08;9(1):556.
PMID: 29422604 DOI: 10.1038/s41467-018-02942-5

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

Matched MeSH terms: Pancreatic Neoplasms/genetics*
Fulltext Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, et al.

Oncotarget, 2016 Oct 11;7(41):66328-66343.
PMID: 27579533 DOI: 10.18632/oncotarget.11041

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

Matched MeSH terms: Pancreatic Neoplasms/genetics*
Paracrine IL-6 signaling mediates the effects of pancreatic stellate cells on epithelial-mesenchymal transition via Stat3/Nrf2 pathway in pancreatic cancer cells

Wu YS, Chung I, Wong WF, Masamune A, Sim MS, Looi CY

Biochim Biophys Acta Gen Subj, 2017 Feb;1861(2):296-306.
PMID: 27750041 DOI: 10.1016/j.bbagen.2016.10.006

BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process.
METHODS: Gene expression of IL-6 and IL-6Rα in PSC and PDAC cells was measured with qRT-PCR. The role of PSC-secreted IL-6, JAK/Stat3 signaling, and Nrf2 mediation on EMT-related genes expression was also examined with qRT-PCR. EMT phenotypes were assessed with morphological change, wound healing, migration, and invasion.
RESULTS: PSC expressed higher mRNA levels of IL-6 but lower IL-6Rα compared to PDAC cells. Neutralizing IL-6 in PSC secretion reduced mesenchymal-like morphology, migration and invasion capacity, and mesenchymal-like gene expression of N-cadherin, vimentin, fibronectin, collagen I, Sip1, Snail, Slug, and Twist2. Inhibition of JAK/Stat3 signaling induced by IL-6 repressed EMT and Nrf2 gene expression. Induction of Nrf2 activity by tert-butylhydroquinone (tBHQ) increased both EMT phenotypes and gene expression (N-cadherin, fibronectin, Twist2, Snail, and Slug) repressed by IL-6 neutralizing antibody. Simultaneous inhibition of Nrf2 expression with siRNA and Stat3 signaling further repressed EMT gene expression, indicating that Stat3/Nrf2 pathway mediates EMT induced by IL-6.
CONCLUSIONS: IL-6 from PSC promotes EMT in PDAC cells via Stat3/Nrf2 pathway.
GENERAL SIGNIFICANCE: Targeting Stat3/Nrf2 pathway activated by PSC-secreted IL-6 may provide a novel therapeutic option to improve the prognosis of PDAC.

Matched MeSH terms: Pancreatic Neoplasms/metabolism*; Pancreatic Neoplasms/pathology
Green synthesis of gold nanoparticles from Scutellaria barbata and its anticancer activity in pancreatic cancer cell (PANC-1)

Wang L, Xu J, Yan Y, Liu H, Karunakaran T, Li F

Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):1617-1627.
PMID: 31014134 DOI: 10.1080/21691401.2019.1594862

Nanotechnology has been materialized as a proficient technology for the development of anticancer nanoparticles all the way through an environment-friendly approach. Conventionally, nanoparticles have been assembled by dissimilar methods, but regrettably rely on the negative impact on the natural environment. Amalgamation of nanoparticles by means of plant extract is alternate conservative methods. Scutellaria barbata species was used majorly as food or as medicines against various diseases, and extensive research was conducted for their therapeutic properties. The present research was mainly focused on the synthesis of gold nanoparticles from the Scutellaria barbata by green route method and evaluation of its anticancer activity against pancreatic cancer cell lines (PANC-1). The gold nanoparticles have been characterized by UV-visible spectroscopy, TEM, SAED, AFM, and FTIR analysis. The synthesized gold nanoparticles (AuNPs) possessed effective anticancer activity against pancreatic cancer cell lines (PANC-1). Hence, further research on this plant may lead to the development of novel anticancer drugs which can be used to combat pancreatic cancer.

Matched MeSH terms: Pancreatic Neoplasms/pathology*
Fulltext Bilio-enteric anastomoses: results in benign and malignant conditions

Toufeeq Khan TF, Lwin M, Ulah S, Zahari A, Mokti I

Singapore Med J, 1993 Dec;34(6):545-50.
PMID: 8153721

Twenty bilio-enteric anastomoses were performed or managed from May 1990 to December 1992. Recurrent pyogenic cholangitis (RPC) and pancreatic cancer were the commonest conditions which required drainage procedures. Roux-en-Y hepatico-jejunostomy (RHJ) was performed in 9 patients, 4 for RPC, one for pancreatic cancer, another for a cholangiocarcinoma, 2 following excision of choledochal cyst and one hepatico-jejunostomy was part of a Whipple reconstruction. Roux-en-Y side to side choledocho-jejunostomy (CDJ) was performed in one patient. Choledocho-duodenostomy (CDD) was performed in 6, 4 for obstructive jaundice due to choledocholithiasis, one for RPC and one in a choledochal cyst. One patient operated elsewhere presented with complications after a CDD. Palliative cholecysto-jejunostomy (CYJ) was carried out in 4 patients with pancreatic malignancy. All benign conditions were treated by hepatico-jejunostomy and choledocho-duodenostomy, while three patients with malignant conditions were treated by hepatico-jejunostomy. Permanent subcutaneous access loops were provided when recurrent problems were anticipated, 4 in RPC and one after subtotal resection of a cholangiocarcinoma. Based on this study, we found Roux-en-Y hepatico-jejunostomy a versatile drainage procedure, which was useful in both benign and malignant diseases.

Matched MeSH terms: Pancreatic Neoplasms/surgery*
Fulltext Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, et al.

Cancer Res, 2020 Sep 15;80(18):4004-4013.
PMID: 32641412 DOI: 10.1158/0008-5472.CAN-20-0447

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Matched MeSH terms: Pancreatic Neoplasms/genetics*
Fulltext Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, et al.

Nat Genet, 2015 Aug;47(8):911-6.
PMID: 26098869 DOI: 10.1038/ng.3341

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Matched MeSH terms: Pancreatic Neoplasms/genetics*
Fulltext Traditional and Novel Adiposity Indicators and Pancreatic Cancer Risk: Findings from the UK Women's Cohort Study

Shyam S, Greenwood D, Mai CW, Tan SS, Mohd Yusof BN, Moy FM, et al.

Cancers (Basel), 2021 Mar 02;13(5).
PMID: 33801191 DOI: 10.3390/cancers13051036

(1) Background: We studied the association of both conventional (BMI, waist and hip circumference and waist-hip ratio) and novel (UK clothing sizes) obesity indices with pancreatic cancer risk in the UK women's cohort study (UKWCS). (2) Methods: The UKWCS recruited 35,792 women from England, Wales and Scotland from 1995 to 1998. Cancer diagnosis and death information were obtained from the National Health Service (NHS) Central Register. Cox's proportional hazards regression was used to evaluate the association between baseline obesity indicators and pancreatic cancer risk. (3) Results: This analysis included 35,364 participants with a median follow-up of 19.3 years. During the 654,566 person-years follow up, there were 136 incident pancreatic cancer cases. After adjustments for age, smoking, education and physical activity, each centimetre increase in hip circumference (HR: 1.03, 95% CI: 1.01-1.05, p = 0.009) and each size increase in skirt size (HR: 1.12, 95% CI: 1.02-1.23, p = 0.041) at baseline increased pancreatic cancer risk. Baseline BMI became a significant predictor of pancreatic cancer risk (HR: 1.04, 95% CI: 1.00-1.08, p = 0.050) when latent pancreatic cancer cases were removed. Only baseline hip circumference was associated with pancreatic cancer risk (HR: 1.03, 95% CI: 1.00-1.05, p = 0.017) when participants with diabetes at baseline were excluded to control for reverse causality. (4) Conclusion: Hip circumference and skirt size were significant predictors of pancreatic cancer risk in the primary analysis. Thus, hip circumference is useful to assess body shape relationships. Additionally, standard skirt sizes offer an economical and objective alternative to conventional obesity indices for evaluating pancreatic cancer risk in women.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Key drug-targeting genes in pancreatic ductal adenocarcinoma

Sakharkar MK, Dhillon SK, Mazumder M, Yang J

Genes Cancer, 2021;12:12-24.
PMID: 33884102 DOI: 10.18632/genesandcancer.210

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal type of cancer. In this study, we undertook a pairwise comparison of gene expression pattern between tumor tissue and its matching adjacent normal tissue for 45 PDAC patients and identified 22 upregulated and 32 downregulated genes. PPI network revealed that fibronectin 1 and serpin peptidase inhibitor B5 were the most interconnected upregulated-nodes. Virtual screening identified bleomycin exhibited reasonably strong binding to both proteins. Effect of bleomycin on cell viability was examined against two PDAC cell lines, AsPC-1 and MIA PaCa-2. AsPC-1 did not respond to bleomycin, however, MIA PaCa-2 responded to bleomycin with an IC50 of 2.6 μM. This implicates that bleomycin could be repurposed for the treatment of PDAC, especially in combination with other chemotherapy agents. In vivo mouse xenograft studies and patient clinical trials are warranted to understand the functional mechanism of bleomycin towards PDAC and optimize its therapeutic efficacy. Furthermore, we will evaluate the antitumor activity of the other identified drugs in our future studies.

Matched MeSH terms: Pancreatic Neoplasms
Combined chemotherapy and EUS-guided intra-tumoral 32-P implantation for locally advanced pancreatic ductal adenocarcinoma: a pilot study

Naidu J, Bartholomeusz D, Zobel J, Safaeian R, Hsieh W, Crouch B, et al.

Endoscopy, 2021 Jan 13.
PMID: 33440437 DOI: 10.1055/a-1353-0941

AIM: This study evaluated clinical outcomes of combined chemotherapy and Endoscopic Ultrasound (EUS) guided intra-tumoral radioactive phosphorus-32 (32P OncoSil) implantation in locally advanced pancreatic adenocarcinoma (LAPC).
METHODS: Consecutive patients with a new histological diagnosis of LAPC were recruited over 20 months. Baseline CT and 18FDG PET-CT were performed and repeated after 12 weeks to assess response to treatment. Following 2 cycles of conventional chemotherapy, patients underwent EUS-guided 32P OncoSil implantation followed by a further six cycles of chemotherapy.
RESULTS: Twelve patients with LAPC (8M:4F; median age 69 years, IQR 61.5-73.3) completed the treatment. Technical success was 100% and no procedural complications were reported. At 12 weeks, there was a median reduction of 8.2cm3 (95% CI 4.95-10.85; p=0.003) in tumour volume, with minimal or no 18FDG uptake in 9 (75%) patients. Tumour downstaging was achieved in 6 (50%) patients, leading to successful resection in 5 (42%) patients, of which 4 patients (80%) had clear (R0) resection margins.
CONCLUSIONS: EUS guided 32P OncoSil implantation is feasible and well tolerated and was associated with a 42% rate of surgical resection in our cohort. However, further evaluation in a larger randomized multicenter trial is warranted. (32P funded by OncoSil Medical Ltd, equipment and staff funded by the Royal Adelaide Hospital, ClinicalTrials.gov number, NCT03003078).

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Almajali B, Al-Jamal HAN, Taib WRW, Ismail I, Johan MF, Doolaanea AA, et al.

Pharmaceuticals (Basel), 2021 Apr 16;14(4).
PMID: 33923474 DOI: 10.3390/ph14040369

To date, natural products are widely used as pharmaceutical agents for many human diseases and cancers. One of the most popular natural products that have been studied for anticancer properties is thymoquinone (TQ). As a bioactive compound of Nigella sativa, TQ has shown anticancer activities through the inhibition of cell proliferation, migration, and invasion. The anticancer efficacy of TQ is being investigated in several human cancers such as pancreatic cancer, breast cancer, colon cancer, hepatic cancer, cervical cancer, and leukemia. Even though TQ induces apoptosis by regulating the expression of pro- apoptotic and anti-apoptotic genes in many cancers, the TQ effect mechanism on such cancers is not yet fully understood. Therefore, the present review has highlighted the TQ effect mechanisms on several signaling pathways and expression of tumor suppressor genes (TSG). Data from relevant published experimental articles on TQ from 2015 to June 2020 were selected by using Google Scholar and PubMed search engines. The present study investigated the effectiveness of TQ alone or in combination with other anticancer therapeutic agents, such as tyrosine kinase inhibitors on cancers, as a future anticancer therapy nominee by using nanotechnology.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Potential of Anti-Cancer Activity of Secondary Metabolic Products from Marine Fungi

Noman E, Al-Shaibani MM, Bakhrebah MA, Almoheer R, Al-Sahari M, Al-Gheethi A, et al.

J Fungi (Basel), 2021 May 30;7(6).
PMID: 34070936 DOI: 10.3390/jof7060436

The promising feature of the fungi from the marine environment as a source for anticancer agents belongs to the fungal ability to produce several compounds and enzymes which contribute effectively against the cancer cells growth. L-asparaginase acts by degrading the asparagine which is the main substance of cancer cells. Moreover, the compounds produced during the secondary metabolic process acts by changing the cell morphology and DNA fragmentation leading to apoptosis of the cancer cells. The current review has analyed the available information on the anticancer activity of the fungi based on the data extracted from the Scopus database. The systematic and bibliometric analysis revealed many of the properties available for the fungi to be the best candidate as a source of anticancer drugs. Doxorubicin, actinomycin, and flavonoids are among the primary chemical drug used for cancer treatment. In comparison, the most anticancer compounds producing fungi are Aspergillusniger, A.fumigatusA.oryzae, A.flavus, A. versicolor, A.terreus,Penicilliumcitrinum, P.chrysogenum, and P.polonicum and have been used for investigating the anticancer activity against the uterine cervix, pancreatic cancer, ovary, breast, colon, and colorectal cancer.

Matched MeSH terms: Pancreatic Neoplasms
Recent advances and prospects in gemcitabine drug delivery systems

Paroha S, Verma J, Dubey RD, Dewangan RP, Molugulu N, Bapat RA, et al.

Int J Pharm, 2021 Jan 05;592:120043.
PMID: 33152476 DOI: 10.1016/j.ijpharm.2020.120043

Cancer is a community health hazard which progress at a fatal rate in various countries across the globe. An agent used for chemotherapy should exhibit ideal properties to be an effective anticancer medicine. The chemotherapeutic medicines used for treatment of various cancers are, gemcitabine, paclitaxel, etoposide, methotrexate, cisplatin, doxorubicin and 5-fluorouracil. However, many of these agents present nonspecific systemic toxicity that prevents their treatment efficiency. Of all, gemcitabine has shown to be an active agent against colon, pancreatic, colon, ovarian, breast, head and neck and lung cancers in amalgamation with various anticancer agents. Gemcitabine is considered a gold-standard and the first FDA approved agent used as a monotherapy in management of advanced pancreatic cancers. However due to its poor pharmacokinetics, there is need of newer drug delivery system for efficient action. Nanotechnology has shown to be an emerging trend in field of medicine in providing novel modalities for cancer treatment. Various nanocarriers have the potential to deliver the drug at the desired site to obtain information about diagnosis and treatment of cancer. This review highlights on various nanocarriers like polymeric nanoparticles, solid lipid nanoparticles, mesoporous silica nanoparticles, magnetic nanoparticles, micelles, liposomes, dendrimers, gold nanoparticles and combination approaches for delivery of gemcitabine for cancer therapy. The co-encapsulation and concurrent delivery of Gem with other anticancer agents can enhance drug action at the cancer site with reduced side effects.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Cross-sectional descriptive study of management modalities and quality of life of surgical patients in a palliative care unit

Amjad, N.M., Karim, K.A., Naing Soe, Y.

International Medical Journal Malaysia, 2016;15(1):35-43.
MyJurnal

Introduction: The goal of palliative care is the provision of the best quality of life (QOL) for terminally ill
and dying patients. Advances in medical treatment has seen an increase in overall survival of all stages of
malignant diseases. This includes advanced and/or inoperable malignancies where management is mainly
palliative involving different modalities. Methods: We designed a cross-sectional descriptive study of
surgical patients in a palliative care unit in a 1000-bedded teaching hospital in Kuantan, Malaysia.
Objectives of this study are: to study the demographic characteristics and indications for admission of
surgical patients in palliative care unit, to study the options of treatment modalities and their
complications, to identify the barriers in decision making in surgical treatment and finally to objectively
assess the quality of life of these patients by utilizing QUALITY OF LIFE (WHOQOL) –BREF –questionnaire.
Results: One hundred and one eligible patients (53%) male, (47%) female of mean age of 54yrs, majority
Malay and Chinese patients were included in the study. All patients had malignancies and they were Breast
(30%), Lower gastrointestinal (GI) (24%), (18%) upper GI, (15%) hepato-biliary, and (7%) pancreatic cancers.
Thirty two percents of patients had emergency treatment while the rest had supportive treatment. Barriers
to decision making were mainly due to patient factors in 71%, while 12% was due to the disease presenting
at an advanced stage and 15% due to limitation of care. The final results of overall quality of life rating
were shown as poor (1%), neither poor nor good (42%), good (52%) and very good (2%). Conclusions:
Palliative care and end of life decision making from surgical point of view is a delicate issue. Like all other
fields in medicine, palliative care must be evidence-based with specific goal directed therapy. Our study
shows that we are able to positively impact the quality of life in more than two thirds of our patients. Our
aim is to achieve 100% success. As such, it is imperative to inculcate the goal of palliative care to all grades
of health care personnel. ‘To cure sometimes, To relieve often, To comfort always’ should not be mere
words.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Toxicological studies of Orthosiphon stamineus (Misai Kucing) standardized ethanol extract in combination with gemcitabine in athymic nude mice model

Yehya AHS, Asif M, Kaur G, Hassan LEA, Al-Suede FSR, Abdul Majid AMS, et al.

J Adv Res, 2019 Jan;15:59-68.
PMID: 30581613 DOI: 10.1016/j.jare.2018.05.006

Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of Orthosiphon stamineus (O.s) and its marker compound (rosmarinic acid) in combination with gemcitabine. O.s (200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext A ten-year retrospective analysis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Malaysia

Gunavathy M, Rohana AG, Norlela S, Nor Azmi K

Med J Malaysia, 2014 Jun;69(3):133-7.
PMID: 25326355 MyJurnal

Gastroenteropancreatic neuroendocrine tumours (GEP- nETs) are rare neoplasms with a complex spectrum of presentation. The study cohort (n=64) included the diagnoses of carcinoid, (n=26, 41%), insulinoma, (n=25, 39%), undetermined (n=10, 16%), VIPoma, glucagonoma and multiple endocrine neoplasia (MEn-1) (n= 3). Almost half of the patients (n=31) had distant metastasis at diagnosis, the commonest being carcinoid tumours. Presenting symptoms were due to either hormonal expressions or mass effects. diagnoses in all patients were made based on positive immunohistochemical staining for chromogranin and synaptophysin. Less than half (n=30) had either serum chromogranin A, urinary 5-hydroxyindole acetic acid (5-hIAA), serum insulin or C-peptide levels performed. Commonest diagnostic imaging modalities were computed tomography (CT) scan (94%) and abdominal ultrasound (15%). Curative or palliative surgery was performed in 58 patients. Systemic therapy included long acting somatostatin analogues (n=14), chemotherapy (n=7) and interferon-α2b (n=1). nine patients died, all of who had metastatic disease at diagnosis. All patients with insulinoma (n=25) were assessed by endocrinologists whilst carcinoid tumours were mainly managed by surgeons (n=16/26). Involvements of oncologists and gastroenterologists were minimal. This study showed that patients with GEP-nETs in Malaysia commonly presented late in the disease with presence of distant metastases. Less than half had adequate hormonal and biochemical examinations performed for diagnostic as well as prognostic purposes, and only a third received systemic therapy. Lack of institutionalbased database, clinical expertise and multi-disciplinary involvement contributed to the inadequate surveillance and management of the disease.

Matched MeSH terms: Pancreatic Neoplasms
Fulltext Novel Semi-Synthetic Cu (II)-Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

Hossan MS, Break MKB, Bradshaw TD, Collins HM, Wiart C, Khoo TJ, et al.

Molecules, 2021 Apr 09;26(8).
PMID: 33918814 DOI: 10.3390/molecules26082166

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.

Matched MeSH terms: Pancreatic Neoplasms/pathology*

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