Olaparib was the first poly ADP-ribose polymerase inhibitor approved for patients with cancer with mutations in either BRCA1 or BRCA2 in China. To the best of our knowledge, however, no study has described the efficacy of olaparib for patients with breast cancer with double mutations in BRCA1 and BRCA2. The present case report describes a patient with breast cancer with deleterious germline mutations in both BRCA1 and BRCA2. The 56-year-old patient with multiple metastatic breast cancer underwent breast cancer resection with 12 years interval between removal of the left and right breast. Germline mutations in both BRCA1 (S405X) and BRCA2 (W2990X) were identified by NGS. She received two cycles of chemotherapy with a combination of albumin-bound paclitaxel and capecitabine; the response was progressive disease. Subsequently, the patient was treated with a gradual dosage of decreasing olaparib (600 to 300 mg BID) for 6 months until grade 3 anemia could not be alleviated by giving erythropoietin and iron, and CT imaging showed a partial response (35% reduction). The patient then switched to exemestane therapy due to the continuous grade 3 anemia. In conclusion, the present study reported a female patient with double heterozygosity of BRCA1 and BRCA2 who benefited from olaparib monotherapy. Thus, olaparib may be a suitable treatment for such patients.

Background: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. Methods: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. Results: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. Conclusions: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.

Purpose To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. Methods In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu ® , generic doxorubicin hydrochloride liposome) 40 mg/m 2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Results Of 44 enrolled patients (median age, 53.5 years; range, 34–69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3–4.1) and median OS was 15.0 months (95% CI 12.1–17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. Conclusion PLD (Duomeisu ® ) 40 mg/m 2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

Background: Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2- Chinese advanced breast cancer patients. Method: HR+/HER2- advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. Result: In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2- metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.

OBJECTIVE:To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis.METHODS:The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy. The result was analyzed in combination with clinicopathological data.RESULTS:The proportion of regulatory T cells (Treg) after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034). The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survival (OS). The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg, which was 23.5 and 9.4 months respectively (P<0.05).CONCLUSION:The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

Trastuzumab has been widely used among the breast cancer patients with human epidermal growth factor receptor 2 (HER2) overexpression. The genetically engineered trastuzumab traded as Cipterbin® was developed in China since 2003. We have disclosed the phase I clinical trial data of safety, pharmacokinetic profile (PK) in patients with metastasis breast cancer. Subjects identified as HER2 strong positive received single intravenously doses of 100, 250 or 500 mg Cipterbin® in dose-escalation manner. The safety evaluations were recorded and plasma concentration profiles for the drug were analyzed. 27 Chinese metastatic breast cancer patients were enrolled in this study. Patients in each group of different dosage were well-tolerated. The most frequently drug-related adverse events were fever (59.3 %), transaminase increased (22.2 %), chills (18.5 %) and arrhythmia (18.5 %). Only one patient with severe adverse event was observed in 250 mg group revealing brachycardia. PK profile analysis showed that sera steady concentration could be reached in dose-proportional manner, except volume of distribution (Vd) and clearance (CL), which reached peak values at 250 mg administration cohort. This genetically engineered HER2-target antibody had demonstrated the accepted safety with well-tolerated.

BACKGROUND The shifts to second-line chemotherapy for metastatic breast cancer (MBC) were widely required based on pharmaceutical molecular profiles to reach out precision medicine. The emerging precise treatment of cancer requires the implementation of clarified pharmacogenetic profiles which are capable of elucidating the predictive responses to cancer chemotherapy. Therefore we were interested in the analysis of the roles of single nucleotide polymorphism (SNP) of GSTP1 (glutathione S-transferase pi 1 gene) alleles to identify pharmacological links with predictors of clinical responses and toxicities. METHODS 93 MBC patients receiving thiotepa plus docetaxel chemotherapy were enrolled in this study. Optimized CYP3A5, CYP2B6, and GSTP1 were predominantly selected as candidate genes and their three SNPs (CYP2B6 G516T, CYP3A5 A6986G, and GSTP1 A313G) were genotyped by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF) mass spectrometry. Progression-free survival (PFS), disease control rate, and chemo-related toxicities were recorded. RESULTS GSTP1 A313G (rs1695) was identified to be related with disease progression. In particular, patients harboring AG/GG genotype demonstrated a statistically longer PFS than those with AA. Multivariate analysis confirmed that AG/GG genotype was associated with both clinical responses and liver-localized metastatic lesions. No correlation was found between these three SNPs and chemotherapy-induced toxicity. CONCLUSIONS These results suggest that the GSTP1 polymorphism is a novel prognostic marker for clinical response to thiotepa-containing chemotherapy regimens. Such evidence could provide insight into the role of pharmacogenetics to deprive of biases in shifting regimens solely by empirical choices.

Objective: This study aimed to assess the prognostic value of CD4(+)CD25(+) T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy.Methods: 217 patients participated in the follow-up study. CD4(+)CD25(+) proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of f CD4(+)CD25(+) proportion more than 5% and less than or equal to 5% in peripheral T cells.Results: Peripheral f CD4(+)CD25(+) T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral f CD4(+)CD25(+) proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95% CI 1.04, 2.62). Above 5% f CD4(+)CD25(+) proportion of T cells produced the HR to be 1.76 (95% CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95% CI 1.05, 12.29) in triple negative breast cancer patients.Conclusion: Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral f CD4(+)CD25(+) T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

Synchronous breast cancer and breast lymphoma are rare. It is of high rate of misdiagnosis in clinical practice. Here we present two cases with this presentation. They are both middle-aged women, with stage I invasive ductal carcinoma of the breast. One patient happened to have primary breast lymphoma (PBL); the other was secondary breast lymphoma (SBL). Their pathology and immunohistochemistry (IHC) findings supported the diagnosis of multiple primary carcinoma. Both patients had a surgery. Then they both received CHOP regime chemotherapy and subsequent endocrine therapy.

1040 Background: UTD1, a genetically engineered epothilone analog, is a microtubule stabilizing agent that showed promising activities in phase I trials. In this report, two open-label, multicenter phase II studies of UTD1 alone or UTD1 plus capecitabine (CAP) were carried out to evaluate its efficacy and safety in metastatic breast cancer (MBC) patients (pts). Methods: In both studies, MBC patient who was pretreated with taxanes, anthracyclines and/or CAP received UTD1 at a dose of 40mg/m2/d intravenously on day 1 to day 5 or at 30mg/m2/d (d1-d5) in combination with CAP (2000mg/m2/d, orally) on d1-d14, every 21 days until disease progression or unacceptable toxicity occurred for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) and the secondary endpoints were toxicity and progression-free survival (PFS) for the combination. Results: 25 pts received a total of 128 cycles in the combination with a median of 6 cycles (range 1-6 cycles) per patient. Among 24 pts who were evaluable for efficacy, responses included one complete response (CR), 11 partial responses (PR), 9 stable diseases (SD), and a median PFS of 7.5 months. In the UTD1 monotherapy, 34 pts received a median of 4 cycles of UTD1 and 30 pts were evaluable for efficacy. One patient had a confirmed CR, 7 had PR and 13 had SD. Peripheral neuropathy (PN) was the major adverse event associated with UTD1 toxicity in both studies, but was manageable. 40% of pts in the combination had grade 3 PN or/and foot syndrome compared to 11% in the monotherapy. One patient was removed from the monotherapy after the first cycle because of grade 3 neurotoxicity, which was reversed after 3 weeks. There were no drug-related deaths in the two studies. Other grade 3 toxicities included neutropenia (12% vs 3%, combination vs monotherapy), diarrhea (4% vs 3%), myalgia/arthralgia (8% vs 0%), dizziness (4% vs 0 %). Conclusions: UTD1 was well-tolerated in both studies with the primary toxicity being PN, and demonstrated notable antitumor activities in MBC pts. 27% of ORR was seen for the monotherapy or 50% of ORR and a median PFS of 7.5 months for the combination. A multicenter, phase III study of UTD1 plus CAP vs CAP alone in MBC is underway. Clinical trial information: TRC-13004205.

OBJECTIVE To investigate the efficacy and safety of capecitabine maintenance therapy (MT) after initial capecitabine plus docetaxel (XT) chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). METHODS Fifty-five mTNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients (MT), while 23 patients remained without any treatment (non-MT). We compared progression-free survival (PFS) and safety of both groups. RESULTS The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months (P=0.032), respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant (P=0.003). Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups. CONCLUSIONS After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in mTNBC patients.

Abstract The successful predictively treatment of metastatic breast cancer (MBC) remains a major challenge. Until now there is no definite marker to distinguish responder from non-responder and more and more important, metastasis occurred within different organs lead to serious variations of overall survival. In this study, paclitaxel and anthracyclines pretreated153 patients with MBC received 606 cycles of docetaxel plus thiotepa. 65 of 153 patients were concurrently diagnosed as MBC involved liver metastasis (LM). Among 153 patients, the response were 1 complete response (CR) (0.7%), 25 partial responses (PR) (16.3%), 73 stable diseases (SD) (47.7%), 46 progressive diseases (PD) (30.1%) and 8 unevaluable(5.2%). For LM patients, the localized liver response were 2 CR (3.1%), 20 PR (30.8%), 16 SD (24.6%), 22 PD (33.8%),5 unevaluable (7.7%). Median PFS and OS for both entire and LM subgroup were 6.5 (95% CI, 5.6 to 7.4) versus 4.2 (95%CI, 2.3-6.1), and 20.0 (95% CI, 15.6 to 24.4) versus 14.2 (95%CI, 9.5-18.9) months respectively. 79 SNPs in CYP450, whose minor allele frequency were ≥ 10% were genotyped. There was no significant difference of SNPs in therapeutic responses, PFS or OS. Of importance, there were two distinctive SNPs, rs2277119 and rs4646487 *2/*3 alleles, which tended to have the better liver metastases response than *1 when choosing a false discovery rate as 12%. It seemed that docetaxel plus thiotepa might be regarded as an active specific regimen for MBC with liver metastasis. The generation of conceptually specific chemotherapy targeting the organ with cancer metastasis should be considered in the future. Citation Format: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly. Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2013-5298 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

PURPOSE:To ascertain the biologic significance of lung cancer Side population (SP) cells, which represent putative cancer stem cells (CSC) in the absence of consensus biomarkers for tumor-specific CSC.MATERIALS AND METHODS:We sorted and analyzed the angiogenic features of SP cells, isolated from tumor cell lines based on the exclusion of the DNA dye Hoechst 33342, from the NSCLC cell lines A549 and H460.RESULTS:Compared with non-SP cells, mRNA of vascular endothelial growth factor (VEGF)-A, VEGF-B, angiopoietin (ang)-1, ang-2, fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8) were over-expressed in SP cells accompanied by over-expression of ABCG2 and MDR1 mRNA. The supernatant of cultured SP cells could significantly induce migration of human umbilical vein endothelial cells, while recombinant human endostatin (Endostar 25(®)) could inhibit the migration.CONCLUSIONS:This study revealed that the NSCLC SP cells might represent CSCs and possess pro-angiogenic properties, and antiangiogenesis represent a potential therapy.

BACKGROUND:Increasing evidence shows that bone marrow stromal cells (BMSCs) have antitumor activities both in vitro and in animal models. Further studies fleshed out the supportive data that the antitumor activity of BMSCs could be markedly enhanced by cytokines such as IL-2 and IFN-β (interferon). However, powerful strategies to activate BMSCs other than by genetically engineering interventions are still required.METHODS:In this study, new methods of generating antitumor activities of murine marrow-originated MSCs pulsed with homologous tumor-derived exosomes (TEX) were explored to yield potent immune effectors against hepatocellular carcinoma cells in vitro.RESULTS:The results showed that BMSCs pulsed with exosomes and IFN-γ exhibited increased migration ability with a result of 163.22 ± 26.90 versus 129.89 ± 29.28 cells/HP by transwell determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma cells line H(22) cells by exosomes pulsed BMSCs was significantly increased by 41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that the cell cycle of H(22) cells was arrested in G(0)/G(1) phase. Meanwhile, western blot analysis showed that PCNA protein expression in the supernatant of H(22) cells was significantly decreased.CONCLUSIONS:This study demonstrated that BMSCs pulsed with TEX could enhance its antitumor activities, which might be regarded as a novel promising antitumor treatment.

OBJECTIVE:To infect dendritic cells (DC) by recombinant human adeno-associated virus (rh-AAV) vector with CEA gene to generate antigen-specific CTL cells in vitro and to assay the CEA specific cytotoxic T lymphocyte(CTL), response to CD44(+)CD24(-/low) breast cancer stem cells.METHODS:Peripheral blood mononuclear cells were induced to generate DCs by cytokines interleukin-4(IL-4), granulocyte-macrophage colony-stimulating factor(GM-CSF)and tumor necrosis factor-alpha(TNF-α) while T lymphocytes were cultured with cytokines interleukin-2(IL-2). DCs were infected by CEA gene containing rh-AAV. After being matured, DCs were co-cultured with T cells to generate CTL cells. CD44(+)CD24(-/low) breast cancer stem cells were sorted out from MCF-7 and MDA-MB-231 cells. CEA specific CTL response to CD44(+)CD24(-/low) breast cancer stem cells was assayed by MTT method.RESULTS:The percentages of CD44(+)CD24(-/low) breast cancer stem cells subsets in MCF-7 and MDA-MB-231 were 5.1% and 76.3% respectively. DCs transfected with CEA gene could induce CEA antigen CTLs response. The killing ratio of MCF-7 cells in CEA gene transfection group was 46.5% plusmn; 15.0% with significant difference (P=0.009) as compared with that of CEA gene untransfection group. As for CD44(+)CD24(-/low) breast cancer stem cells subset from MCF-7 cells, CEA gene transfection group resulted in a higher killing ratio of 44.7% ± 28.2% as compared with that of CEA untransfection group. While the inhibitory rate of non-breast cancer stem cells subset from MCF-7 cells in CEA gene transfection group was 50.6% ± 22.2% (P=0.05). CTL cells generated by DCs transfected with CEA gene did not show inhibitory activity to MDA-MB-231 breast cancer cells (without CEA expression) as compared with CEA gene untransfection group. It was the same in CD44(+)CD24(-/low) breast cancer stem cells subset and non-breast cancer stem cells subset from MDA-MB-231 breast cancer cells (P>0.05).CONCLUSION:DCs infected by rh-AAV with CEA gene could induce antigen-specific CTL response to kill CEA expressing breast cancer cells involved in CD44(+)CD24(-/low) breast cancer stem cells subset. It suggests that immune therapy might be a potential treatment of breast cancer stem cells.

BACKGROUND & OBJECTIVE:Advanced pancreatic cancer has a poor prognosis. Gemcitabine (GEM) can improve the quality of life of pancreatic cancer patients. However, the efficacy of gemcitabine-based combination chemotherapy is uncertain. This study was to compare the efficacy of GEM-based combination therapy and GEM alone on advanced pancreatic cancer.METHODS:Clinical data of 40 patients with pathologically or clinically diagnosed advanced pancreatic cancer were analyzed. Of the 40 patients, 15 were treated with GEM (1,000 mg/m(2)) alone weekly for 7 weeks followed by a 2-week rest, then received cycles of 3-week administration with 1-week rest; 25 were treated with GEM (1,000 mg/m(2)) weekly for 2 weeks plus 5-fluorouracil (5-FU) (425-600 mg/m(2)) as bolus at Day 1-5 or 120-hour infusion every 21 days, or cisplatin (DDP) (30-37.5 mg/m(2)) at Day 1-2 every 21 days, or oxaliplatin (85-130 mg/m(2)) at Day 1 every 21 days, or capecitabine (1,000 mg/m(2)) twice a day at Day 1-14 every 21 days, respectively. The survival was analyzed by Kaplan-Meier method. Median time to progression (mTTP), clinical benefit response (CBR), disease control rate, median overall survival (mOS) and toxicity were assessed according to World Health Organization criteria.RESULTS:The rate of CBR was 56.0% in GEM-combination group and 46.7% in GEM alone group. There were no significant differences in disease control rate, mOS, CBR, and adverse events between the two groups (all P>0.05). However, for the patients with stage III-IV advanced pancreatic cancer, the disease control rate was higher in GEM-combination group than in GEM alone group (75.0% vs. 45.5%, P=0.13).CONCLUSION:GEM-combination regimens and GEM alone have similar efficacy, and lead to similar clinical benefit response and mOS for the patients with advanced pancreatic cancer.

Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC.