Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Gene Transfer Techniques ; Humans ; Mesenchymal Stem Cells ; Neoplasms ; therapy ; Paclitaxel ; administration & dosage ; Research ; trends

Metastasis is one of the main reasons causing death in cancer patients. It was reported that chemotherapy might induce metastasis. In order to uncover the mechanism of chemotherapy-induced metastasis and find solutions to inhibit treatment-induced metastasis, the relationship between epithelial-mesenchymal transition (EMT) and doxorubicin (DOX) treatment was investigated and a redox-sensitive small interfering RNA (siRNA) delivery system was designed. DOX-related reactive oxygen species (ROS) were found to be responsible for the invasiveness of tumor cells in vitro, causing enhanced EMT and cytoskeleton reconstruction regulated by Ras-related C3 botulinum toxin substrate 1 (RAC1). In order to decrease RAC1, a redox-sensitive glycolipid drug delivery system (chitosan-ss-stearylamine conjugate (CSO-ss-SA)) was designed to carry siRNA, forming a gene delivery system (CSO-ss-SA/siRNA) downregulating RAC1. CSO-ss-SA/siRNA exhibited an enhanced redox sensitivity compared to nonresponsive complexes in 10 mmol/L glutathione (GSH) and showed a significant safety. CSO-ss-SA/siRNA could effectively transmit siRNA into tumor cells, reducing the expression of RAC1 protein by 38.2% and decreasing the number of tumor-induced invasion cells by 42.5%. When combined with DOX, CSO-ss-SA/siRNA remarkably inhibited the chemotherapy-induced EMT in vivo and enhanced therapeutic efficiency. The present study indicates that RAC1 protein is a key regulator of chemotherapy-induced EMT and CSO-ss-SA/siRNA silencing RAC1 could efficiently decrease the tumor metastasis risk after chemotherapy.
Amines/chemistry* ; Antineoplastic Agents/adverse effects* ; Breast Neoplasms/pathology* ; Chitosan/chemistry* ; Doxorubicin/adverse effects* ; Drug Delivery Systems ; Epithelial-Mesenchymal Transition/drug effects* ; Female ; Humans ; MCF-7 Cells ; Neoplasm Metastasis/prevention & control* ; Oxidation-Reduction ; RNA, Small Interfering/administration & dosage* ; Reactive Oxygen Species/metabolism* ; rac1 GTP-Binding Protein/physiology*

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) μm and (248±149) μm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.
Acrylates ; Animals ; Doxorubicin/administration & dosage* ; Embolization, Therapeutic/methods* ; Microspheres ; Particle Size ; Rabbits

To determine clinical and pathologic profiles for anaplastic large cell lymphoma (ALCL).
 Methods: The clinical data of 22 patients with ALCL were analyzed retrospectively. Therapentie effect of different treatment strategies on ALCL was evaluated.
 Results: The median age for these patients was 32(9-70) years old and the patients with positive ALK accounted for 68.2% (15/22). All patients underwent chemotherapy, including regiments of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CHOPE (CHOP plus etoposide) or BEACOP (CHOP plus etoposide and bleomycin). Fourteen (63.6%) patients achieved initial complete remission (CR) and the CR rate for patients with ALK+ was significantly higher than that of patients with ALK- (P<0.05), while the age, gender, stage, beta 2-microglobulin (2-MG) level, lactate dehydrogenase (LDH) level, B symptoms had no significant effect on the rate of CR (P>0.05). After a median follow-up of 41 (2-150) months, 12 patients were overall survival, the median progression free time was 22.5 (2-150) months, and the age, gender, stage, IPI index, ALK expression level, beta 2-MG level, LDH level, and B symptoms had no significant effect on the rate of overall survival (P>0.05).
 Conclusion: ALK-positive occurs mainly in ALCL patients. The chemotherapy is still the main treatment, and CHOPE regimen is a better initial treatment scheme because the most patients show good prognosis.
Adolescent ; Adult ; Age Factors ; Aged ; Alkaline Phosphatase ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bleomycin ; administration & dosage ; Child ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Etoposide ; administration & dosage ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; drug therapy ; enzymology ; mortality ; Male ; Middle Aged ; Prednisone ; administration & dosage ; Prognosis ; Retrospective Studies ; Sex Factors ; Treatment Outcome ; Vincristine ; administration & dosage ; Young Adult

Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.
Adenosine Triphosphatases ; Carcinoma, Non-Small-Cell Lung ; Doxorubicin ; Drug Resistance, Multiple* ; Drug Therapy ; Humans ; In Vitro Techniques* ; Leukemia ; Lymphoma ; Parents ; Phosphorylation ; Phosphotransferases ; Rhodamine 123 ; United States Food and Drug Administration

OBJECTIVETo explore the clinical efficacy and safety of rituximab combined with fludarabine and cyclophosphamide for the treatment of the chronic lymphocytic leukemia (CLL).

METHODSForty cases of CLL patients treated in our hospital from March 2010 to March 2014 years were selected and divided into the observation group (20 cases) and control group (20 cases) by random number table method. The patients in control group were treated with CHOP chemotherapy, the patients in observation group were treated with rituximab combined with fludarabine, cyclophosphamide treatment. The therapeutic efficacy of patients in 2 groups was analyzed according to the peripheral hemogram indexes, symptom and sign disappeared time as well as adverse reaction incidence.

RESULTSthe remission rate in observation group was 90.00%, which was significantly higher than that in control group (70.00%) (P < 0.05); the peripheral hemogram indexes in 2 groups before treatment showed no significant difference (P > 0.05), and were significantly improved after treatment, but the white blood cell count and lymphocyte absolute number were significantly lower in observation group as compared to the control group (P < 0.05); symptom and sign disappeared time in observation group were significantly shorter as compared with the control group (P < 0.05); adverse reaction incidence in obseovation group was significantly lower as compared with control group (P < 0.05).

CONCLUSIONapplication of rituximab combined with fludarabine and cyclophosphamide in the treatment of CLL shows the higher curative effect, can effectively improve the symptoms and reduce the incidence of adverse reactions. It is worthy to be popularized.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Doxorubicin ; therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Prednisone ; therapeutic use ; Rituximab ; administration & dosage ; therapeutic use ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Vincristine ; therapeutic use

The present study was designed to determine the mechanism underlying the treatment of nephrotic syndrome using astragaloside by observing the effects of astragaloside on the expression of nephrin and podocin proteins and genes in kidneys of rats with adriamycin nephropathy. The rats were injected with adriamycin and, after successful model establishment, randomly divided into a model group, a Methylprednisolone (MP) group, and an astragaloside group. The 24-h complete urine samples were collected. Biochemical indicators were monitored, and kidney tissues were collected for pathological analysis using light microscopy and electron microscopy. The mRNA expression of nephrin and podocin was measured in the kidney tissues using the real-time qPCR, and the protein expression levels of nephrin and podocin were detected using Western blot analysis. At the end of 12 weeks of drug intervention, the urinary protein level was lower in the MP and astragaloside groups than that in the model group (P = 0.008 and P = 0.01, respectively). Serum albumin was higher in the MP and astragaloside groups than in the model group (P < 0.001 and P = 0.012, respectively). Podocytes in the MP group were nearly normal, and fusion of podocytes in the astragaloside group was significantly less than that in the control group. The nephrin and podocin mRNA and protein expression levels in the intervention groups were higher (P < 0.05) than that in the model group. Due to the increased expression of podocyte-related nephrin and podocin proteins, astragaloside maintained slit diaphragm integrity and decreased the level of proteinuria in rats with adriamycin nephropathy.
Animals ; Astragalus Plant ; chemistry ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; Glucosides ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; chemically induced ; drug therapy ; Male ; Podocytes ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVETo explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor.

METHODSThe clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed.

RESULTSNine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one patient treated with chemotherapy alone was still alive after 11 months of follow-up.

CONCLUSIONSDesmoplastic small round cell tumor is a very rare, special type of soft tissue tumor, with very poor prognosis. This tumor may be preliminarily diagnosed according to the imaging characteristics and detection of tumor markers, however, final diagnosis is made by pathology. Surgery is the priority of treatment, combined with complementary radiation and chemotherapy.

Abdominal Neoplasms ; complications ; diagnosis ; mortality ; therapy ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; analysis ; Carboplatin ; administration & dosage ; Child ; Combined Modality Therapy ; methods ; Cyclophosphamide ; administration & dosage ; Desmoplastic Small Round Cell Tumor ; complications ; diagnosis ; mortality ; therapy ; Doxorubicin ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; analysis ; Prognosis ; Retrospective Studies

OBJECTIVETo summarize the experience of the chemotherapy regimen cisplatin + fluorouracil + vincristine (C5V) for hepatoblastoma, and analyze the factors associated the outcome.

METHODA retrospective analysis was conducted for the outcome of hepatoblastoma. Sixty-three patients who received the regimen of C5V as the first choice of chemotherapy were reviewed, including 37 males and 26 females. The age at diagnosis ranged from 2 days after birth to 124 months, median 15 months. Four patients with stage I, 16 patients with stage II, 28 patients with stage III, 15 patients with stage IV disease were enrolled in the study. Nine patients had primary tumor resection while the remain by 54 received neoadjuvant chemotherapy. The median follow-up time was 30 months.

RESULTForty patients had delayed surgery, including 35 patients with regimen C5V alone, the others were treated with regimen C5V and cisplatin + adriamycin (CITA). The mean time of neojuvant chemotherapy was (3.4 ± 1.7) cycles. The mean time of chemotherapy after surgery was (5.3 ± 2.0) cycles. In 12 cases the (24.5%) tumor recurred after surgery. The margin of resection less than 0.5 cm , vascular invasion, stage III or IV disease were all the high risks of relapse (P = 0.049,0.001,0.022, respectively). Two-year overall survival (OS) and 5-year OS of the study was 61.1% and 58.7%, respectively. The 2-year OS and 5-year OS of stage I to III were 75.0% and 75.0%, 100.0% and 100.0%, 65.8% and 61.4%. The 1-year OS and 3-year OS of stage IV was 20.0%, 13.3%, respectively. Univariate analysis showed that age at diagnosis less than 60 months, vascular invasion, thrombocythemia at diagnosis, stage III or IV, tumor resection was the prognostic factor (P = 0.019, <0.001,0.011, <0.001, respectively). Multivariate analysis showed that tumor resection and age at diagnosis less than 60 months were both the prognostic factor (P < 0.001, 0.004, respectively ).

CONCLUSIONThe regimen of C5V is useful for hepatoblastoma. Tumor resection is the key factor of treatment. Prognostic factor is composed of age, stage, and clinical sign at diagnosis.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cisplatin ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Hepatoblastoma ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Liver Neoplasms ; drug therapy ; Male ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Retrospective Studies ; Vincristine ; administration & dosage