Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Ramakrishnan, P.; Loh, Wei Mee; Gopinath, Subash C.B.; Bonam, Srinivasa Reddy; Fareez, Ismail M.; Guad, Rhanye Mac; Sim, Maw Shin; Wu, Yuan Seng

doi:10.1016/j.apsb.2019.11.008

Cited by 60 publications

(39 citation statements)

References 136 publications

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“…The high expression of the multidrug resistance genes in pancreatic cancer cells makes pancreatic cancer less sensitive to chemotherapy. Currently, gemcitabine-based chemotherapy is considered to be the first-line standard treatment for advanced pancreatic cancer, but the response rate of systemic intravenous chemotherapy for gemcitabine alone is only 5%e10% (37,38). The chemotherapy was performed through arterial infusion, and there were no obvious complications of biliary tract infection.…”

Section: Discussionmentioning

confidence: 99%

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

et al. 2021

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Insertion of radioactive strips through the biliary stent has been reported to offer longer survival and patency than an uncovered conventional self-expanding metal stent in patients with unresectable malignant biliary obstruction. The aim of this study was to investigate the safety and effectiveness of intraluminal brachytherapy combined with 125 I seed implantation and transarterial infusion chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice. METHOD: From October 2012 to January 2018, 21 consecutive patients diagnosed with biliary obstruction caused by locally advanced, nonmetastatic pancreatic cancer with cytologically or histologically confirmed by biopsy were enrolled and receive treatment with intraluminal brachytherapy using 125 I seed strand and CT-guided percutaneous radioactive seed implantation therapy. The procedure-related and radiation complications were assessed. The outcomes were measured in terms of stent patency, patient survival, complications related to the procedure. RESULT: One of the 22 patients (4.5%, 1/22) with pancreatic head cancer failed to perform the above procedure because the guidewire was unable to pass through the obstruction segment. The remaining 21 patients (95.5%, 21/22) with pancreatic head cancer with obstructive jaundice were successfully placed with biliary stents and radioactive strips through drainage tubes. The median number of 125 I seeds loaded was 15, ranging from 12 to 17. After the chemotherapy with gemcitabine and cisplatin, no adverse reaction of Grade III~Ⅳ occurred in all cases. Median stent patency was 12.50 months (95% CI: 10.26, 14.74). By May 2019, all 21 patients had died, with overall survival of 5.2e23.3 months, with a median survival of 13.20 months (95% CI: 10.96, 15.44). CONCLUSION: Percutaneous 125 I seed implantation combined with insertion of radioactive strips through the biliary stent has the characteristics of less trauma, fewer complications, simple operation, and so on. These procedures bring remission of obstructive jaundice combined with the increased survival for the treatment of obstructive jaundice caused by unresectable pancreatic head cancer if follow-up chemotherapy is carried out. The long-term efficacy of this treatment combination needs to be confirmed by further multicenter, large sample size prospective randomized controlled studies.

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Section: Discussionmentioning

confidence: 99%

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

et al. 2021

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“…Phytochemicals have been proposed as modulators/inhibitors of the desmoplastic reaction in PDAC in many previous publications (recently reviewed by Ramakrishnan et al [ 220 ]).…”

Section: Discussionmentioning

confidence: 99%

Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer

Koltai¹,

Reshkin

Carvalho

et al. 2021

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Present-day treatments have not shown real improvements in reducing the high mortality rate and the short survival of the disease. The average survival is less than 5% after 5 years. New innovative treatments are necessary to curtail the situation. The very dense pancreatic cancer stroma is a barrier that impedes the access of chemotherapeutic drugs and at the same time establishes a pro-proliferative symbiosis with the tumor, thus targeting the stroma has been suggested by many authors. No ideal drug or drug combination for this targeting has been found as yet. With this goal in mind, here we have explored a different complementary treatment based on abundant previous publications on repurposed drugs. The cell surface protein CD44 is the main receptor for hyaluronan binding. Many malignant tumors show over-expression/over-activity of both. This is particularly significant in pancreatic cancer. The independent inhibition of hyaluronan-producing cells, hyaluronan synthesis, and/or CD44 expression, has been found to decrease the tumor cell’s proliferation, motility, invasion, and metastatic abilities. Targeting the hyaluronan-CD44 pathway seems to have been bypassed by conventional mainstream oncological practice. There are existing drugs that decrease the activity/expression of hyaluronan and CD44: 4-methylumbelliferone and bromelain respectively. Some drugs inhibit hyaluronan-producing cells such as pirfenidone. The association of these three drugs has never been tested either in the laboratory or in the clinical setting. We present a hypothesis, sustained by hard experimental evidence, suggesting that the simultaneous use of these nontoxic drugs can achieve synergistic or added effects in reducing invasion and metastatic potential, in PDAC. A non-toxic, low-cost scheme for inhibiting this pathway may offer an additional weapon for treating pancreatic cancer.

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“…Cancer. GC is one of GI cancers that contribute to high mortality due to late diagnosis [3,77]. Intriguingly, Gao et al suggested that lncRNA UCA1 could be a potential diagnostic and biomarker target in the early stage of GC, owing to the fact that highly expressed lncRNA UCA1 can be easily found in the plasma of GC patients and therefore provides simplicity for sample extraction [42].…”

Section: Gastricmentioning

confidence: 99%

Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions

Ramli

Sim

Guad

et al. 2021

Journal of Oncology

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The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

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Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Cited by 60 publications

References 136 publications

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer

Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions

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