Single-institution experience with gemcitabine–cisplatin combination therapy as a second-line treatment for patients with unresectable biliary tract cancer after failure of gemcitabine–S-1 combination therapy: a prospective feasibility study

Matsuyama, Ryusei; Morioka, Daisuke; Mori, Rintaro; Hiratani, Seigo; Yabushita, Yasuhiro; Ota, Yoshihide; Kumamoto, Takafumi; Taniguchi, Koichi; Endo, Itaru

doi:10.1007/s00280-018-3566-z

Cited by 6 publications

(2 citation statements)

References 27 publications

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“…Gemcitabine has been widely introduced to the treatments of cancers and has been proved as a curative drug alone or combined with other drugs, including cisplatin [ 1–3 ]. However, resistance to gemcitabine in cancer patients occurs commonly, which deters the curative effect [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1β/Wnt/β-catenin signaling pathway

et al. 2020

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Abstract Background: Gemcitabine is widely used in the treatment of breast cancer (BC). However, the resistance to drugs remains a tough concern. The study explored the potential mechanism concerning gemcitabine resistance in triple-negative BC (TNBC) in vitro. Methods: TNBC cells (TNBCC) and gemcitabine-resistance cell lines (GRC) were used. We investigated the sensitivity to gemcitabine responsive to regulation of Nod-like receptor protein 3 (NLRP3) expression in TNBCC in different gemcitabine concentrations. RT-PCR checked NLRP3 mRNA expression and MTT assessed the cell cytotoxicity. Gemcitabine resistance was studied in GRC exposed to 0, 1, 3, 5 nm gemcitabine after GRC were treated with NLRP3 agonist Nigericin sodium salt (NSS) or antagonist CY-09. Epithelial-to-mesenchymal transition (EMT) biomarkers were evaluated via RT-PCR and inflammasome IL-1β, β-catenin content and GSK-3β activity were measured by ELISA methods. Last, we inactivated the signaling and examined the NLRP3, EMT mRNA expression by RT-PCR, IL-1β, β-catenin content and GSK-3β activity by ELISA and cell cytotoxicity through MTT. Results: NLRP3 up-regulation improved cell survival and reduced sensitivity to gemcitabine (P<0.05). NLRP3 had higher expression in GRC than TNBCC. GRC cell viability dropped as the gemcitabine concentration increased. NLRP3 up-regulation added to resistance to gemcitabine in GRC (P<0.05). NLRP3 agonist might induce EMT process, activate wnt/β-catenin signaling and IL-1β, while inactivation of wnt/β-catenin signaling could result in the inhibition of NLRP3, IL-1β and EMT as well as cell viability in GRC (P<0.05). Conclusion: NLRP3 could enhance resistance to gemcitabine via IL-1β/EMT/Wnt/β-catenin signaling, which suggested that NLRP3 antagonist CY-09 might be incorporated into gemcitabine treatment for TNBC.

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Section: Introductionmentioning

confidence: 99%

NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1β/Wnt/β-catenin signaling pathway

et al. 2020

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“…We could not have determined NAC regimen until recently mainly because the standard chemotherapeutic regimen for BTC did not exist at that time when we initiated the NAC program. In other words, we used gemcitabine-S-1 combination (GS) as the NAC regimen at the beginning of the program because the Japanese social insurance coverage of cisplatin for BTC was not approved [47]. However, soon after we initiated the NAC program, gemcitabine-cisplatin combination (GC) was addressed as the standard first-line chemotherapy for patients with BTC ineligible for surgery in the Japanese clinical guidelines as revised in 2013.…”

Section: Discussionmentioning

confidence: 99%

Our Rationale of Initiating Neoadjuvant Chemotherapy for Hilar Cholangiocarcinoma: A Proposal of Criteria for “Borderline Resectable” in the Field of Surgery for Hilar Cholangiocarcinoma

et al. 2018

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Background The concept of ''borderline resectable'' was recently introduced to the field of surgery for pancreatic cancer, and surgical outcomes for this disease with extremely dismal prognosis have improved since the introduction of this concept. However, no such concept has yet been introduced to the field of surgery for hilar cholangiocarcinoma (HCca). Aim To determine a definition and criteria for ''borderline resectable'' in the field of surgery for HCca. Patients and methods Retrospective analysis of 88 patients undergoing curative-intent surgery for HCca at our institution between May 1992 and December 2008 to clarify independent prognostic factors. Results Survival outcomes were obtained for these 88 patients, with a 5-year overall survival rate of 31.8%. Independent factors predictive of cancer death were determined by multivariate analysis to be the presence of regional lymph node metastasis (LNM) and pathological confirmed vascular invasion (VI). Cumulative survival rates of 23 patients with both LNM and VI who underwent surgery were significantly worse than those of the remaining 65 surgically treated patients and similar to those of 26 patients who were considered to have unresectable disease and treated with non-surgical multidisciplinary treatment during the same study period. Conclusion Outcomes of surgery for cases of HCca showing regional LNM and VI were no better than those of nonsurgical treatment for unresectable disease. Coexistence of these two factors indicates oncologically dismal condition and thus such cases should be considered ''borderline resectable.'' Treatments additional to surgery are required for ''borderline resectable'' cases to obtain better outcomes.

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Combination versus mono-therapy as salvage treatment for advanced biliary tract cancer: A comprehensive meta-analysis of published data

Jin

Chen

2019

Critical Reviews in Oncology/Hematology

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Single-institution experience with gemcitabine–cisplatin combination therapy as a second-line treatment for patients with unresectable biliary tract cancer after failure of gemcitabine–S-1 combination therapy: a prospective feasibility study

Abstract: Although some issues remain to be clarified, mainly due to the small sample size, this single-institution experience with GC as second-line treatment after failure of GS showed acceptable outcomes and good tolerability.

Cited by 6 publications

References 27 publications

NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1β/Wnt/β-catenin signaling pathway

NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1β/Wnt/β-catenin signaling pathway

Our Rationale of Initiating Neoadjuvant Chemotherapy for Hilar Cholangiocarcinoma: A Proposal of Criteria for “Borderline Resectable” in the Field of Surgery for Hilar Cholangiocarcinoma

Combination versus mono-therapy as salvage treatment for advanced biliary tract cancer: A comprehensive meta-analysis of published data

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