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Objective: To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer. Methods: Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison. Results: Patients who received trastuzumab-based therapy( n =294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab( n =177) (84.4% vs. 72.4%, χ²=4.095, P =0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P> 0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ²=5.340, P =0.021), but they had similar OS (91.4% vs. 89.1%, χ²=1.008, P =0.315). Conclusions: TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

Objective: To investigate the effects and mechanism of metformin (Met) combined the interleukin-12 (IL-12) on inhibiting hepatoma HepG2 cell proliferation via in vitro and in vivo assays., Materials and Methods: MTT assay was used to detect inhibitory effects of Met, IL-12 alone or combination on HepG2 cells proliferation. Half inhibitory concentration (IC50) and combination index (CI) were also calculated. Anti-tumor effects of combination or monotherapy on the HepG2-bearing mice were investigated and protein expression levels of apoptosis, as well as the Akt/mTOR/STAT3 signaling pathway-related factors were detected by Western blot., Results: MTT results showed that the inhibitory effect of Met combined with IL-12 on HepG2 cell proliferation was significantly enhanced (both p<0.01) compared with monomer therapy group with a significant synergistic effect (CI<1). The apoptosis rate of HepG2 cells treated with Met combined with IL-12 were 88.12±7.15% and significantly higher than the others (all p<0.01). Moreover, combination treatment significantly suppressed hepatoma growth and increased the survival rate of HepG2-bearing mice without evident body weight loss. Western blot analysis showed that Met combined with IL-12 significantly increased the expression of autophagy-related marker proteins, downregulated the protein expression levels of Bcl-2, p-Akt, p-mTOR, p-STAT3, upregulated the expression level of BAX in both HepG2 cells and tumor tissues., Conclusions: Met combined with IL-12 exhibited a synergistic antitumor effect on hepatoma HepG2 cells, and the mechanism may be related to its common inhibition of Akt/mTOR/STAT3 signaling pathway and increase of autophagy in HepG2-bearing mice.

Objective: To investigate the role of miR-21 on multidrug resistance (MDR) in non-small cell lung cancer(NSCLC)and to provide experimental and theoretical basis for MDR reversal., Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to determine the mRNA level of miR-21 both in the chemo-sensitivity cell strain A549 and the chemo-resistance cell strain A549/DDP (primary A549/DDP cells). The miR-21 interference sequence was synthesized and transfected into A549/DDP cells by liposome as the carrier. The miR-21 expression level was knocked down and the change of chemo-sensitivity of cells was detected. Effects of miR-21 on the cell apoptosis and cell cycle in miR-21-depleted A549/DDP cells were analyzed by flow cytometry to elucidate the involvement of miR-21 in MDR reversal in NSCLC. The expression of multidrug-resistant proteins Survivin, Cyclin D1, Epidermal growth factor receptor (EGFR), Multidrug resistance-associated protein1 (MRP1) and Lipoprotein receptor-related protein (LRP) were detected by Western blot., Results: MiR-21 level in multidrug-resistant NSCLC cell line A549/DDP was (5.223±0.316) folds higher than that in A549 cell line (t=48.318, P<0.01). Knockdown of miR-21 in A549/DDP cells significantly reversed their sensitivity to cis-DDP, meanwhile, the value of half maximal inhibitory concentration was significantly decreased compared with control group transfected with empty vector ((22.2±1.2) and (48.6±3.2) μmol/L, t=5.608, P<0.01). Cell apoptosis rate in A549/DDP cell with knockdown of miR-21 was significantly increased compared with primary A549/DDP cell line ((27.7±1.1) % and (16.8±1.1) %, t=10.183, P<0.01). Cell cycle G0/G1 phase in A549/DDP cell with knockdown of miR-21 was significantly decreased compared with primary A549/DDP cell line ((37.5±1.2) % and (43.4±2.3) %, t=8.202, P<0.01). Compared with primary A549/DDP cell line, the expression of Survivin, Cyclin D1, EGFR, MRP1 and LRP in A549/DDP cell with knockdown of miR-21 were significantly decreased ((71.7±4.3)%, t=8.325, P<0.01; (69.4±4.5)%, t=5.162, P<0.01; (52.3±3.2)%, t=8.042, P<0.01; (60.6±4.2)%, t=6.641, P<0.01; (72.9±3.8)%, t=4.566, P<0.01, respectively)., Conclusion: miR-21 silencing reverses the multidrug resistance in lung cancer cell via accelerating cell apoptosis and modulating multidrug resistance-related gene expression. miR-21 may be a potential therapeutic candidate in multidrug resistance patients with lung cancer.

The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).

In this study, we examined the effect of cetuximab (epidermal growth factor receptor monoclonal antibody) combined with afatinib (epidermal growth factor receptorand human epidermal growth factor receptor 2 tyrosine kinase irreversible inhibitor) on the apoptosis of A549 cells and on kinase domain receptor (KDR) and aquaporin 1 (AQP1) expression in A549 cells. A549 cells were cultured in RPMI-1640 and then divided into 4 groups: control group, 1-nM cetuximab group, 25-μM afatinib group, and 1-nM cetuximab + 25-μM afatinib group. After incubation for 48 h, the cell inhibition rate, cell cycle distribution, and invasive ability of A549 cells before and after treatment were examined using MTT, flow cytometry, and transwell assays, respectively. Gene and protein expression levels of KDR and AQP1 were detected by reverse transcription-polymerase chain reaction and western blot analysis. Cetuximab and afatinib significantly inhibited A549 cell growth. Their combination produced greater growth inhibition (P < 0.01). Cetuximab and afatinib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P < 0.01). Compared with monotherapy, cetuximab in combination with afatinib induced G1 phase arrest and downregulated the gene and protein expression of KDR and AQP1 (P < 0.05). Cetuximab in combination with afatinib synergistically inhibited the growth and migration of cells and downregulated the gene and protein expression of KDR and AQP1, indicating that a combination of cetuximab and afatinib is a potential strategy for lung cancer therapy.

Cancer is a complex disease with interactions between normal and neoplastic cells. Since current therapies for cancer largely rely on drugs or radiation that kill dividing cells or block cell division, these treatments may have severe side effects on normal proliferating cells in patients with cancer. Recently, immunotherapeutic approaches for cancer therapy, by which monoclonal antibodies (Mabs) target tumor specific antigens, have shown great potential. Glycoprotein non-metastatic melanoma protein B(Gpnmb)/Osteoactivin (OA) is a transmembrane glycoprotein highly expressed in various types of cancer. Gpnmb/OA promotes the migration, invasion and metastasis of tumor cells. CR 011-vcMMAE is a Mab-drug conjugate being developed for the treatment of Gpnmb/OA-expressing cancers. Gpnmb/OA represents an attractive target in cancer immunotherapy and CR011-vcMMAE holds promise as a reagent in targeted therapy for Gpnmb/OA-expressing malignancies.

Background: Potassium channel blockers have been shown to possess antitumor properties, but the role of apoptosis remains to be clarified. In this study, we investigated the antiproliferative effect of tetraethylammonium (TEA), a nonspecific potassium channel blocker, in rat C6 and 9L glioma cells., Methods: Cytotoxicity was evaluated by MTT assay. Apoptosis was detected by TUNEL and annexin V-FITC/propidium iodide assays. Protein levels were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) levels were assessed flow cytometrically., Results: TEA (2-60 mM) significantly inhibited the proliferation of C6 and 9L glioma cells. In addition, increased cell apoptosis was confirmed after treatment with 40 mM TEA. Apoptosis was associated with a dramatic increase in ROS levels and altered Bcl-2/Bax protein balance., Conclusion: TEA can inhibit proliferation and induce apoptosis in both cell lines; therefore, it might be associated with the increase in intracellular ROS production., (Copyright 2009 S. Karger AG, Basel.)

Telomere maintenance is essential for cancer growth. Induction of telomere dysfunction, for example, by inhibition of telomeric proteins or telomerase, has been shown to strongly enhance cancer cells' sensitivity to chemotherapies. However, it is not clear whether modulations of telomere maintenance constitute cancer cellular responses to chemotherapies. Furthermore, the manner in which anti-cancer drugs affect telomere function remains unknown. In this study, we show that anthracyclines, a class of anti-cancer drugs widely used in clinical cancer treatments, have an active role in triggering telomere dysfunction specifically in telomerase-positive cancer cells. Anthracyclines interrupt telomere maintenance by telomerase through the downregulation of PinX1, a protein factor responsible for targeting telomerase onto telomeres, thereby inhibiting telomerase association with telomeres. We further demonstrate that anthracyclines downregulate PinX1 by inducing this protein degradation through the ubiquitin-proteasome-dependent pathway. Our data not only reveal a novel action for anthracyclines as telomerase functional inhibitors but also provide a clue for the development of novel anti-cancer drugs based on telomerase/telomere targeting, which is actively investigated by many current studies. [ABSTRACT FROM AUTHOR]