Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Yamamura, Jun; Masuda, Norikazu; Yamamoto, Daigo; Tsuyuki, Shigeru; Yamaguchi, Masahide; Tanaka, Satoru; Tsurutani, Junji; Tokunaga, Shinya; Yoshidome, Katsuhide; Mizutani, Masaki; Aono, Toyokazu; Ooe, Asako; Tanino, Hirokazu; Matsunami, Nobuki; Yasojima, Hiroyuki; Nakayama, Takahiro; Nishida, Yukihiro

doi:10.1159/000475879

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…A nucleoside analog known as gemcitabine is integrated into the DNA strands of cancer cells during the S-phase [ 45 , 46 ]. In the process of DNA synthesis, it inhibits the production of deoxynucleotide triphosphates (dNTPs) by the enzyme ribonucleotide reductase [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

Hour,

Tsai,

Lai

et al. 2023

BioMedicine

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Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38’s principal targets, as determined via in silico target screening with network prediction. HMJ-38 also inhibited EGFR kinase activity and EGFR-associated signaling in MIA-GR100 cells. HMJ-38 may be an effective chemotherapeutic adjuvant for gemcitabine-resistant pancreatic cancer cells, in which it induces an antitumor response.

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Section: Discussionmentioning

confidence: 99%

Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

Hour,

Tsai,

Lai

et al. 2023

BioMedicine

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“…This finding was not inferior to other regimens. 19 – 22 The EMBRACE study reported a median PFS of 3.7 months for a median number of prior regimens of 4, including neoadjuvant and adjuvant regimens. However, if we focused on the group of patients who received no more than four regimens as in the EMBRACE study, the corresponding median PFS was 4 months.…”

Section: Discussionmentioning

confidence: 99%

Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients

Ditsatham

Chitapanarux

Somwangprasert

et al. 2018

OTT

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BackgroundWe report the safety and efficacy of eribulin as a late treatment line in Thai metastatic breast cancer (MBC) patients.Patients and methodsA total of 30 MBC patients treated with eribulin between January 2014 and January 2017 were retrospectively analyzed. The patients were scheduled to receive 1.4 mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients had previously received at least three chemotherapy regimens including anthracycline and taxane. Response rate and progression-free survival (PFS) were analyzed.ResultsThe median age was 56 years (range, 40–74 years), with a median follow-up time of 5.7 months (range, 0.2–25 months). The overall response rate was 30% (nine patients): four patients had triple-negative breast cancer, three patients had luminal B breast cancer and two patients had luminal A breast cancer. The median PFS was 2.9 months (range, 0.2–14 months). The median number of previous chemotherapy regimens was 4 (range, 3–9). Univariate analysis showed that the number of regimens (four or fewer) prior to eribulin was statistically associated with superior PFS (P = 0.009). Multivariate analysis also showed similar statistical association between number of prior regimens (four or fewer) and better PFS adjusted by age group (≥50 years; hazard ratio = 1.29; 95% CI: 1.0–1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine (30%) patients had grade 3 anemia toxicities, and the other common toxicities were leukopenia and neutropenia. Four (13%) patients required dose reduction and 16 (53%) patients required dose delay because of toxicities.ConclusionEribulin is an effective drug for heavily pretreated MBC patients with tolerable toxicities. The benefit was superior in patients who received fewer than four previous chemotherapy regimens.

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“…Studies have shown that GEM acts through multiple antitumor mechanisms, including inhibiting DNA synthesis, killing cells in S phase, suppressing the activation of enzymes related to deoxynucleotide metabolism and inducing apoptosis through the caspase pathway [11,12]. GEM is considered the firstline chemotherapy agent for many malignancies, such as pancreatic cancer, breast cancer and lung cancer [13][14][15][16]. Moreover, GEM is also used off-label for multiple types of tumors, and this type of use is sometimes called exploratory treatment [17,18].…”

Section: Introductionmentioning

confidence: 99%

Deoxyelephantopin induces apoptosis via oxidative stress and enhances gemcitabine sensitivity in vitro and in vivo through targeting the NF-κB signaling pathway in pancreatic cancer

Zhong

Huang

et al. 2020

Aging

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Pancreatic cancer is a highly invasive malignant tumor of the digestive system with an unfavorable prognosis worldwide. This trait is thought to be largely attributed to chemoresistance. Chemotherapy is the only hope for patients with advanced pancreatic cancer. Therefore, seeking new effective chemotherapy drugs has become an urgent need. The purpose of our study was to explore whether deoxyelephantopin (DET), a sesquiterpene lactone, has a potential antitumor effect in pancreatic cancer. Additionally, the antitumor effects of DET alone or in combination with gemcitabine (GEM) and the potential mechanism of this combination were revealed. In vitro experiments showed that DET suppressed the proliferation, invasion and metastasis of pancreatic cancer cells, induced cell apoptosis via oxidative stress, and enhanced GEM sensitivity by inhibiting the NF-κB signaling pathway. Beyond that, in vivo experiments showed that DET not only inhibited pancreatic tumor growth and metastasis but also amplified the antitumor capacity of GEM, which was related to the downregulation of NF-κB and its downstream gene products. In summary, it is possible that DET could be developed as a single agent or combined with conventional chemotherapy drugs to improve the treatment of pancreatic cancer.

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Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Cited by 5 publications

References 31 publications

Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

Efficacy of HMJ-38, a new quinazolinone analogue, against the gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cells

Outcome of eribulin as a late treatment line for Thai metastatic breast cancer patients

Deoxyelephantopin induces apoptosis via oxidative stress and enhances gemcitabine sensitivity in vitro and in vivo through targeting the NF-κB signaling pathway in pancreatic cancer

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