1 Wolpin B, Mayer R: A step forward in the treatment of advanced
biliary tract cancer. New England Journal of Medicine 362(14):
1335-1337, 2019. DOI: 10.1056/NEJMe1001183
2 Azizi A, Lamarca A, McNamara M, Valle J: Chemotherapy for
advanced gallbladder cancer (GBC): A systematic review and
meta-analysis. Critical Reviews in Oncology/Hematology 163:
103328, 2023. DOI: 10.1016/j.critrevonc.2021.103328
3 Misra S, Chaturvedi A, Misra N, Sharma I: Carcinoma of the
gallbladder. The Lancet Oncology 4(3): 167-176, 2023. DOI:
10.1016/S1470-2045(03)01021-0
4 Hindson J: Gemcitabine and cisplatin plus immunotherapy in
advanced biliary tract cancer: a phase II study. Nature Reviews
Gastroenterology & Hepatology 19(5): 280-280, 2022. DOI:
10.1038/s41575-022-00616-8
5 Graeber T, Osmanian C, Jacks T, Housman D, Koch C, Lowe S,
Giaccia A: Hypoxia-mediated selection of cells with diminished
apoptotic potential in solid tumours. Nature 379(6560): 88-91,
2021. DOI: 10.1038/379088a0
6 Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y: Role of
hypoxia in cancer therapy by regulating the tumor
microenvironment. Molecular Cancer 18(1): 157, 2022. DOI:
10.1186/s12943-019-1089-9
7 Guo S, Liu M, Gonzalez-Perez R: Role of Notch and its
oncogenic signaling crosstalk in breast cancer. Biochimica et
Biophysica Acta (BBA) - Reviews on Cancer 1815(2): 197-213,
2021. DOI: 10.1016/j.bbcan.2010.12.002
8 Nwabo K, Takam K, Tagne S, Vecchio L, Seke E, Muller J,
Bassi G, Lukong E, Kumar G, Mbo A, Krampera M:
Developmental pathways associated with cancer metastasis:
Notch, Wnt, and Hedgehog. Cancer Biology & Medicine 14(2):
109, 2022. DOI: 10.20892/j.issn.2095-3941.2016.0032
9 Hill R, Marie-Egyptienne D, Hedley D: Cancer stem cells,
hypoxia and metastasis. Seminars in Radiation Oncology 19(2):
106-111, 2021. DOI: 10.1016/j.semradonc.2008.12.002
2920
10 Hidalgo M: New insights into pancreatic cancer biology. Annals
of Oncology 23: x135-x138, 2020. DOI: 10.1093/annonc/mds313
11 Koch U, Radtke F: Notch and cancer: a double-edged sword.
Cellular and Molecular Life Sciences 64(21): 2746-2762, 2019.
DOI: 10.1007/s00018-007-7164-1
12 Aster J, Pear W, Blacklow S: The varied roles of notch in cancer.
Annual Review of Pathology: Mechanisms of Disease 12(1):
245-275, 2022. DOI: 10.1146/annurev-pathol-052016-100127
13 Allenspach E, Maillard I, Aster J, Pear W: Notch signaling in
cancer. Cancer Biology & Therapy 1(5): 466-476, 2016. DOI:
10.4161/cbt.1.5.159
14 Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin
S, Rodriguez-Carunchio L, Solé M, Thung S, Stanger B, Llovet J:
Notch signaling is activated in human hepatocellular carcinoma
and induces tumor formation in mice. Gastroenterology 143(6):
1660-1669.e7, 2023. DOI: 10.1053/j.gastro.2012.09.002
15 Kopan R, Ilagan M: The canonical notch signaling pathway:
unfolding the activation mechanism. Cell 137(2): 216-233, 2023.
DOI: 10.1016/j.cell.2009.03.045
16 Oka C, Nakano T, Wakeham A, Pompa J, Mori C, Sakai T,
Okazaki S, Kawaichi M, Shiota K, Mak T, Honjo T: Disruption
of the mouse RBP-J kappa gene results in early embryonic
death. Development 121(10): 3291-3301, 2023. DOI:
10.1242/dev.121.10.3291
17 McElhinny A, Li J, Wu L: Mastermind-like transcriptional coactivators: emerging roles in regulating cross talk among
multiple signaling pathways. Oncogene 27(38): 5138-5147,
2022. DOI: 10.1038/onc.2008.228
18 Artavanis-Tsakonas S, Rand M, Lake R: Notch signaling: cell
fate control and signal integration in development. Science
284(5415): 770-776, 2023. DOI: 10.1126/science.284.5415.770
19 Dai G, Deng S, Guo W, Yu L, Yang J, Zhou S, Gao T: Notch
pathway inhibition using DAPT, a γ-secretase inhibitor (GSI),
enhances the antitumor effect of cisplatin in resistant
osteosarcoma. Molecular Carcinogenesis 58(1): 3-18, 2020.
DOI: 10.1002/mc.22873
20 Grottkau B, Chen X, Friedrich C, Yang X, Jing W, Wu Y, Cai X,
Liu Y, Huang Y, Lin Y: DAPT Enhances the Apoptosis of
Human Tongue Carcinoma Cells. International Journal of Oral
Science 1(2): 81-89, 2012. DOI: 10.4248/ijos.08025
21 Li L, Peng Y, Liu Y, Wang L, Wu X: Gastric cancer cell growth
and epithelial-mesenchymal transition are inhibited by γsecretase inhibitor DAPT. Oncology Letters 7(6): 2160-2164,
2018. DOI: 10.3892/ol.2014.1980
22 Onishi H, Yamasaki A, Kawamoto M, Imaizumi A, Katano M:
Hypoxia but not normoxia promotes Smoothened transcription
through upregulation of RBPJ and Mastermind-like 3 in
pancreatic cancer. Cancer Letters 371(2): 143-150, 2018. DOI:
10.1016/j.canlet.2015.11.012
23 Yamasaki A, Onishi H, Imaizumi A, Kawamoto M, Fujimura A,
Oyama Y, Katano M: Protein-bound polysaccharide-K inhibits
hedgehog signaling through down-regulation of MAML3 and RBPJ
transcription under hypoxia, suppressing the malignant phenotype
in pancreatic cancer. Anticancer Res 36(8): 3945-3952, 2016.
24 Matsushita S, Onishi H, Nakano K, Nagamatsu I, Imaizumi A,
Hattori M, Oda Y, Tanaka M, Katano M: Hedgehog signaling
pathway is a potential therapeutic target for gallbladder cancer.
Cancer Science 105(3): 272-280, 2021. DOI: 10.1111/cas.12354
25 Fulawka L, Blaszczyk J, Tabakov M, Halon A: Assessment of
Ki-67 proliferation index with deep learning in DCIS (ductal
Na et al: MAML3-induced GBC Malignancy
26
27
28
29
30
31
32
33
34
35
36
37
38
39
carcinoma in situ). Scientific Reports 12(1): 3166, 2022. DOI:
10.1038/s41598-022-06555-3
Grassi E, Pantazopoulou V, Pietras A: Hypoxia-induced release,
nuclear translocation, and signaling activity of a DLK1
intracellular fragment in glioma. Oncogene 39(20): 4028-4044,
2021. DOI: 10.1038/s41388-020-1273-9
Lei J, Ma J, Ma Q, Li X, Liu H, Xu Q, Duan W, Sun Q, Xu J,
Wu Z, Wu E: Hedgehog signaling regulates hypoxia induced
epithelial to mesenchymal transition and invasion in pancreatic
cancer cells via a ligand-independent manner. Mol Cancer 12:
66, 2013. DOI: 10.1186/1476-4598-12-66
Thiery J, Acloque H, Huang R, Nieto M: Epithelialmesenchymal transitions in development and disease. Cell
139(5): 871-890, 2021. DOI: 10.1016/j.cell.2009.11.007
Cano C, Motoo Y, Iovanna J: Epithelial-to-mesenchymal
transition in pancreatic adenocarcinoma. The Scientific World
JOURNAL 10: 1947-1957, 2016. DOI: 10.1100/tsw.2010.183
Javle M, Zhao H, Abou-alfa G: Systemic therapy for gallbladder
cancer. Chinese Clinical Oncology 8(4): 44-44, 2019. DOI:
10.21037/cco.2019.08.14
Ichimiya S, Onishi H, Nagao S, Koga S, Sakihama K, Nakayama
K, Fujimura A, Oyama Y, Imaizumi A, Oda Y, Nakamura M:
GLI2 but not GLI1/GLI3 plays a central role in the induction of
malignant phenotype of gallbladder cancer. Oncology Reports
45(3): 997-1010, 2021. DOI: 10.3892/or.2021.7947
Rapisarda A, Melillo G: Overcoming disappointing results with
antiangiogenic therapy by targeting hypoxia. Nature Reviews
Clinical Oncology 9(7): 378-390, 2021. DOI: 10.1038/
nrclinonc.2012.64
Maftouh M, Avan A, Sciarrillo R, Granchi C, Leon L, Rani R,
Funel N, Smid K, Honeywell R, Boggi U, Minutolo F, Peters G,
Giovannetti E: Synergistic interaction of novel lactate
dehydrogenase inhibitors with gemcitabine against pancreatic
cancer cells in hypoxia. British Journal of Cancer 110(1): 172182, 2021. DOI: 10.1038/bjc.2013.681
Didiasova M, Schaefer L, Wygrecka M: Targeting GLI
transcription factors in cancer. Molecules 23(5): 1003, 2019.
DOI: 10.3390/molecules23051003
Köchert K, Ullrich K, Kreher S, Aster JC, Kitagawa M, Jöhrens
K, Anagnostopoulos I, Jundt F, Lamprecht B, Zimber-Strobl U,
Stein H, Janz M, Dörken B, Mathas S: High-level expression of
Mastermind-like 2 contributes to aberrant activation of the
NOTCH signaling pathway in human lymphomas. Oncogene
30(15): 1831-1840, 2011. DOI: 10.1038/onc.2010.544
Chang W, Lai A: Aberrations in Notch-Hedgehog signalling
reveal cancer stem cells harbouring conserved oncogenic
properties associated with hypoxia and immunoevasion. British
Journal of Cancer 121(8): 666-678, 2021. DOI: 10.1038/s41416019-0572-9
Marignol L, Rivera-Figueroa K, Lynch T, Hollywood D:
Hypoxia, notch signalling, and prostate cancer. Nat Rev Urol
10(7): 405-413, 2013. DOI: 10.1038/nrurol.2013.110
Patrad E, Niapour A, Farassati F, Amani M: Combination
treatment of all-trans retinoic acid (ATRA) and γ-secretase
inhibitor (DAPT) cause growth inhibition and apoptosis
induction in the human gastric cancer cell line. Cytotechnology
70(2): 865-877, 2018. DOI: 10.1007/s10616-018-0199-3
Qiu K, Ma C, Lu L, Wang J, Chen B, Mao H, Wang Y, Wang H:
DAPT suppresses proliferation and migration of hepatocellular
carcinoma by regulating the extracellular matrix and inhibiting
40
41
42
43
44
45
46
47
48
49
50
51
52
53
the Hes1/PTEN/AKT/mTOR signaling pathway. Journal of
Gastrointestinal Oncology 12(3): 1101-1116, 2021. DOI:
10.21037/jgo-21-235
Abstracts from USCAP 2020: Pancreas, gallbladder, ampulla,
and extra-hepatic biliary tree (1739-1801). Mod Pathol 33: 18081866, 2020.
USCAP: Abstracts: pancreas, gallbladder, ampulla, and extrahepatic biliary tree. Mod Pathol 35(Suppl 2): 1317-1354, 2022.
DOI: 10.1038/s41379-022-01046-2
Bensken W, Ho V, Pieracci F: Basic introduction to statistics in
medicine, Part 2: Comparing data. Surgical Infections 22(6):
597-603, 2023. DOI: 10.1089/sur.2020.430
Kawamoto M, Onishi H, Ozono K, Yamasaki A, Imaizumi A,
Kamakura S, Nakano K, Oda Y, Sumimoto H, Nakamura M:
Tropomyosin-related kinase B mediated signaling contributes to the
induction of malignant phenotype of gallbladder cancer. Oncotarget
8(22): 36211-36224, 2022. DOI: 10.18632/oncotarget.16063
Bhandari V, Hoey C, Liu L, Lalonde E, Ray J, Livingstone J,
Lesurf R, Shiah Y, Vujcic T, Huang X, Espiritu S, Heisler L,
Yousif F, Huang V, Yamaguchi T, Yao C, Sabelnykova V, Fraser
M, Chua M, Van der Kwast T, Liu S, Boutros P, Bristow R:
Molecular landmarks of tumor hypoxia across cancer types.
Nature Genetics 51(2): 308-318, 2022. DOI: 10.1038/s41588018-0318-2
Gilkes D, Semenza G: Role of hypoxia-inducible factors in
breast cancer metastasis. Future Oncology 9(11): 1623-1636,
2022. DOI: 10.2217/fon.13.92
Haider S, McIntyre A, Van Stiphout R, Winchester L, Wigfield
S, Harris A, Buffa F: Genomic alterations underlie a pan-cancer
metabolic shift associated with tumour hypoxia. Genome
Biology 17(1): 140, 2018. DOI: 10.1186/s13059-016-0999-8
Zhang M, Cui J, Lee D, Yuen V, Chiu D, Goh C, Cheu J, Tse A,
Bao M, Wong B, Chen C, Wong C, Ng I, Wong C: Hypoxiainduced macropinocytosis represents a metabolic route for liver
cancer. Nature Communications 13(1): 954, 2022. DOI:
10.1038/s41467-022-28618-9
Zhuravleva E, O’Rourke C, Andersen J: Mutational signatures
and processes in hepatobiliary cancers. Nature Reviews
Gastroenterology & Hepatology 19(6): 367-382, 2022. DOI:
10.1038/s41575-022-00587-w
Briscoe J, Thérond PP: The mechanisms of Hedgehog signalling
and its roles in development and disease. Nat Rev Mol Cell Biol
14(7): 416-429, 2013. DOI: 10.1038/nrm3598
Kikuchi I, Takahashi-kanemitsu A, Sakiyama N, Tang C, Tang
P, Noda S, Nakao K, Kassai H, Sato T, Aiba A, Hatakeyama M:
Dephosphorylated parafibromin is a transcriptional coactivator
of the Wnt/Hedgehog/Notch pathways. Nature Communications
7(1): 12887, 2023. DOI: 10.1038/ncomms12887
Huang S, He J, Zhang X, Bian Y, Yang L, Xie G, Zhang K, Tang
W, Stelter A, Wang Q, Zhang H, Xie J: Activation of the hedgehog
pathway in human hepatocellular carcinomas. Carcinogenesis
27(7): 1334-1340, 2021. DOI: 10.1093/carcin/bgi378
Yeh T, Wu C, Hsu K, Liao W, Yang M, Li A, Wang A, Kuo M,
Chi C: The activated Notch1 signal pathway is associated with
gastric cancer progression through cyclooxygenase-2. Cancer
Research 69(12): 5039-5048, 2022. DOI: 10.1158/00085472.CAN-08-4021
Onishi H, Ichimiya S, Yanai K, Umebayashi M, Nakamura K,
Yamasaki A, Imaizumi A, Nagai S, Murahashi M, Ogata H,
Morisaki T: RBPJ and MAML3: Potential therapeutic targets for
2921
ANTICANCER RESEARCH 43: 2909-2922 (2023)
54
55
56
57
58
59
60
61
62
63
64
65
small cell lung cancer. Anticancer Research 38(8): 4543-4547,
2022. DOI: 10.21873/anticanres.12758
Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S,
Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji
M, Nambu Y, Furuse J, Miyazaki M, Nimura Y: Gemcitabine
alone or in combination with cisplatin in patients with biliary tract
cancer: a comparative multicentre study in Japan. British Journal
of Cancer 103(4): 469-474, 2021. DOI: 10.1038/sj.bjc.6605779
Nabhan C, Gajria D, Krett NL, Gandhi V, Ghias K, Rosen ST:
Caspase activation is required for gemcitabine activity in
multiple myeloma cell lines. Mol Cancer Ther 1(13): 1221-1227,
2002.
Knox J, Hedley D, Oza A, Feld R, Siu L, Chen E, Nematollahi
M, Pond G, Zhang J, Moore M: Combining gemcitabine and
capecitabine in patients with advanced biliary cancer: a phase II
trial. Journal of Clinical Oncology 23(10): 2332-2338, 2022.
DOI: 10.1200/JCO.2005.51.008
Yokoi K, Fidler I: Hypoxia increases resistance of human
pancreatic cancer cells to apoptosis induced by gemcitabine.
Clinical Cancer Research 10(7): 2299-2306, 2023. DOI:
10.1158/1078-0432.ccr-03-0488
Zhang X, Galardi E, Duquette M, Delic M, Lawler J, Parangi S:
Antiangiogenic treatment with the three thrombospondin-1 type
1 repeats recombinant protein in an orthotopic human pancreatic
cancer model. Clinical Cancer Research 11(6): 2337-2344, 2022.
DOI: 10.1158/1078-0432.CCR-04-1900
Wouters A, Pauwels B, Lambrechts H, Pattyn G, Ides J, Baay
M, Meijnders P, Peeters M, Vermorken J, Lardon F: Retention
of the in vitro radiosensitizing potential of gemcitabine under
anoxic conditions, in p53 wild-type and p53-deficient non-smallcell lung carcinoma cells. International Journal of Radiation
Oncology*Biology*Physics 80(2): 558-566, 2023. DOI:
10.1016/j.ijrobp.2010.12.051
Lam W, Bussom S, Cheng Y: Effect of hypoxia on the
expression of phosphoglycerate kinase and antitumor activity of
troxacitabine and gemcitabine in non-small cell lung carcinoma.
Molecular Cancer Therapeutics 8(2): 415-423, 2022. DOI:
10.1158/1535-7163.MCT-08-0692
Doktorova H, Hrabeta J, Khalil M, Eckschlager T: Hypoxiainduced chemoresistance in cancer cells: The role of not only
HIF-1. Biomedical Papers 159(2): 166-177, 2022. DOI:
10.5507/bp.2015.025
Liang C, Shi S, Meng Q, Liang D, Ji S, Zhang B, Qin Y, Xu J,
Ni Q, Yu X: Complex roles of the stroma in the intrinsic
resistance to gemcitabine in pancreatic cancer: where we are and
where we are going. Experimental & Molecular Medicine
49(12): e406-e406, 2021. DOI: 10.1038/emm.2017.255
Qiang L, Wu T, Zhang HW, Lu N, Hu R, Wang YJ, Zhao L,
Chen FH, Wang XT, You QD, Guo QL: HIF-1α is critical for
hypoxia-mediated maintenance of glioblastoma stem cells by
activating Notch signaling pathway. Cell Death Differ 19(2):
284-294, 2012. DOI: 10.1038/cdd.2011.95
Onishi H, Nakamura K, Yanai K, Nagai S, Nakayama K, Oyama
Y, Fujimura A, Ozono K, Yamasaki A: Cancer therapy that
targets the Hedgehog signaling pathway considering the cancer
microenvironment (Review). Oncology Reports 47(5): 93, 2022.
DOI: 10.3892/or.2022.8304
Shih I, Wang T: Notch signaling, gamma-secretase inhibitors,
and cancer therapy. Cancer Research 67(5): 1879-1882, 2022.
DOI: 10.1158/0008-5472.CAN-06-3958
2922
66 Li P, Lin X, Zhang J, Li Y, Lu J, Huang F, Zheng C, Xie J, Wang
J, Huang C: The expression of presenilin 1 enhances
carcinogenesis and metastasis in gastric cancer. Oncotarget 7(9):
10650-10662, 2022. DOI: 10.18632/oncotarget.7298
67 Mori M, Miyamoto T, Yakushiji H, Ohno S, Miyake Y,
Sakaguchi T, Hattori M, Hongo A, Nakaizumi A, Ueda M, Ohno
E: Effects of N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-Sphenylglycine t-butyl ester (DAPT) on cell proliferation and
apoptosis in Ishikawa endometrial cancer cells. Human Cell
25(1): 9-15, 2020. DOI: 10.1007/s13577-011-0038-8
68 Li JY, Li RJ, Wang HD: γ-secretase inhibitor DAPT sensitizes tAUCB-induced apoptosis of human glioblastoma cells in vitro via
blocking the p38 MAPK/MAPKAPK2/Hsp27 pathway. Acta
Pharmacol Sin 35(6): 825-831, 2014. DOI: 10.1038/aps.2013.195
69 Inamura N, Kimura T, Wang L, Yanagi H, Tsuda M, Tanino M,
Nishihara H, Fukuda S, Tanaka S: Notch1 regulates invasion and
metastasis of head and neck squamous cell carcinoma by
inducing EMT through c-Myc. Auris Nasus Larynx 44(4): 447457, 2022. DOI: 10.1016/j.anl.2016.08.003
70 Zhou J, Jain S, Azad A, Xu X, Yu H, Xu Z, Godbout R, Fu Y:
Notch and TGFβ form a positive regulatory loop and regulate
EMT in epithelial ovarian cancer cells. Cellular Signalling 28(8):
838-849, 2020. DOI: 10.1016/j.cellsig.2016.03.016
71 Lin H, Zhang T, Chen M, Shen J: Novel biomarkers for the
diagnosis and prognosis of gallbladder cancer. Journal of
Digestive Diseases 22(2): 62-71, 2021. DOI: 10.1111/17512980.12966
72 Enjoji M, Yamaguchi K, Nakamuta M, Nakashima M, Kotoh K,
Tanaka M, Nawata H, Watanabe T: Movement of a novel serum
tumour marker, RCAS1, in patients with biliary diseases.
Digestive and Liver Disease 36(9): 622-627, 2022. DOI:
10.1016/j.dld.2004.04.006
73 Yang G, Lu Z, Meng F, Wan Y, Zhang L, Xu Q, Wang Z:
Circulating miR-141 as a potential biomarker for diagnosis,
prognosis and therapeutic targets in gallbladder cancer. Scientific
Reports 12(1): 10072, 2022. DOI: 10.1038/s41598-022-13430-8
74 Mehrotra R, Tulsyan S, Hussain S, Mittal B, Singh Saluja S,
Singh S, Tanwar P, Khan A, Javle M, Hassan M, Pant S, De
Aretxabala X, Sirohi B, Rajaraman P, Kaur T, Rath G: Genetic
landscape of gallbladder cancer: Global overview. Mutation
Research/Reviews in Mutation Research 778: 61-71, 2020. DOI:
10.1016/j.mrrev.2018.08.003
75 Aloia T, Járufe N, Javle M, Maithel S, Roa J, Adsay V, Coimbra
F, Jarnagin W: Gallbladder Cancer: expert consensus statement.
HPB 17(8): 681-690, 2018. DOI: 10.1111/hpb.12444
76 Onishi H: Hedgehog signaling pathway as a new therapeutic
target in pancreatic cancer. World Journal of Gastroenterology
20(9): 2335, 2014. DOI: 10.3748/wjg.v20.i9.2335
77 Xu S, Zhan M, Wang J: Epithelial-to-mesenchymal transition in
gallbladder cancer: from clinical evidence to cellular regulatory
networks. Cell Death Discovery 3(1): 17069, 2022. DOI:
10.1038/cddiscovery.2017.69
78 Boutros C, Gary M, Baldwin K, Somasundar P: Gallbladder
cancer: Past, present and an uncertain future. Surgical Oncology
21(4): e183-e191, 2020. DOI: 10.1016/j.suronc.2012.08.002
Received April 21, 2023
Revised May 12, 2023
Accepted May 15, 2023
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