Efficacy and toxicities of doxorubicin plus ifosfamide in the second-line treatment of uterine leiomyosarcoma

PurposeUterine leiomyosarcoma is a rare and aggressive tumor known for its drug resistance and metastatic potential. The standard first-line treatment typically involves anthracycline-based chemotherapy or a combination of gemcitabine and docetaxel; however, there is currently no established second-line treatment. Therefore, the aim of this study was to evaluate the efficacy and toxicity of doxorubicin plus ifosfamide as a potential second-line treatment for uterine leiomyosarcoma.Materials and methodsThis is a retrospective, single-center, single-arm study. We reviewed the tumor registry data from January 2010 to December 2022 and identified patients with uterine leiomyosarcoma who had previously received first-line salvage or adjuvant treatment involving gemcitabine and taxotere, and later experienced tumor recurrence. Patients who met these criteria were included in the study. The primary endpoint was the efficacy of doxorubicin and ifosfamide as a second-line treatment for uterine leiomyosarcoma, as measured by progression-free survival, 1-year overall survival, and response rate. The secondary endpoint was the adverse events associated with this regimen.ResultsFifty-two patients were diagnosed with uterine leiomyosarcoma during the study period, nine of whom were included in the data analysis. All patients had previously received gemcitabine-docetaxel as first-line adjuvant therapy, with a median progression-free survival period of 8.4 months. Doxorubicin-ifosfamide was administered as second-line treatment, with a median progression-free survival of 6.0 months (range: 2.7-79.9 months). The clinical benefit rate of the second-line treatment was 66.7%, with a median overall survival of 33.0 months, and a 1-year overall survival rate of 83.3%. Previous reports have shown that the median progression-free survival for second-line treatments using other regimens ranged from 1.4-5.6 months. The most common adverse event was myelosuppression, with five patients requiring granulocyte colony-stimulating factor and one patient requiring a blood transfusion. No patient discontinued treatment due to unmanageable adverse events.ConclusionUse of doxorubicin with ifosfamide may be a promising and reasonable second-line treatment with manageable adverse events for patients with uterine leiomyosarcoma

External stimulus-responsive biomaterials designed for the culture and differentiation of ES, iPS, and adult stem cells

The physical and chemical characteristics of biomaterial surface and hydrogels can be altered by external stimuli, such as light irradiation, temperature changes, pH shifts, shear stress forces, electrical forces, and the addition of small chemical molecules. Such external stimulus-responsive biomaterials represent promising candidates that have been developed for the culture and differentiation of embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and adult stem cells. Biomaterials that are designed to respond in a reversible manner to specific external signals can be formed on micropatterned or non-micropatterned surface, in hydrogels, or on microcarriers. Stem cells and the cells differentiated from them into specific tissue lineages can be cultured and/or differentiated on dishes with immobilized external stimulus-responsive polymers. Cells can be detached from these dishes without using an enzymatic digestion method or a mechanical method when the appropriate external stimulus is generated on the surface. This review discusses the polymers and polymeric designs employed to produce surface and hydrogels for stem cell culture, differentiation, and/or cell detachment using various external stimuli

Genetic copy number variants in myocardial infarction patients with hyperlipidemia

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is the chief cause of death in Taiwan and many countries, of which myocardial infarction (MI) is the most serious condition. Hyperlipidemia appears to be a significant cause of myocardial infarction, because it causes atherosclerosis directly. In recent years, copy number variation (CNV) has been analyzed in genomewide association studies of complex diseases. In this study, CNV was analyzed in blood samples and SNP arrays from 31 myocardial infarction patients with hyperlipidemia.</p> <p>Results</p> <p>We identified seven CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001), at 1p21.3, 1q31.2 (<it>CDC73</it>), 1q42.2 (<it>DISC1</it>), 3p21.31 (<it>CDCP1</it>), 10q11.21 (<it>RET</it>) 12p12.3 (<it>PIK3C2G</it>) and 16q23.3 (<it>CDH13</it>), respectively. In particular, the CNV region at 10q11.21 was examined by quantitative real-time PCR, the results of which were consistent with microarray findings.</p> <p>Conclusions</p> <p>Our preliminary results constitute an alternative method of evaluating the relationship between CNV regions and cardiovascular disease. These susceptibility CNV regions may be used as biomarkers for early-stage diagnosis of hyperlipidemia and myocardial infarction, rendering them valuable for further research and discussion.</p

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears

AbstractObjectiveTo study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears.Materials and methodsThe medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests.ResultsThe incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14–3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38–0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25–0.44, p<0.0001, respectively).ConclusionsPregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components

Physical cues of cell culture materials lead the direction of differentiation lineages of pluripotent stem cells

Both human pluripotent stem cells (hPSCs) from embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have the potential ability to differentiate into many different cell types originating from all three germ layers. This review discusses physical cues from natural and synthetic biomaterials that guide the differentiation of hESCs and hiPSCs into several different lineages. We place special focus on how the hPSC differentiation fate is affected by (a) the elasticity of biomaterials used for hPSC culture, (b) the topography of biomaterials used for hPSC culture, and (c) the mechanical forces associated with biomaterials (stretching and electrical stimulation via biomaterials) used for hPSC culture

Polymeric design of cell culture materials that guide the differentiation of human pluripotent stem cells

Human pluripotent stem cells (hPSCs), including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), have the potential to differentiate into many cell types that originate from the three germ layers, such as dopamine-secreting cells and insulin-secreting cells for the treatment of Alzheimer's disease and diabetes, respectively. However, it is challenging to guide hPSC differentiation into desired cell lineages due to their varying differentiation ability. A reasonable strategy is to mimic the stem cell microenvironment for the differentiation of hPSCs into specific cell lineages using optimal polymeric biomaterials for hPSC culture. This review summarizes various methods for differentiating hPSCs cultured on polymeric biomaterials and discusses the optimal methods and cell culture polymeric biomaterials for hPSC differentiation into specific cell lineages. The recent trend in protocols avoids embryoid body (EB, aggregated cells) formation because EBs contain different types of cells. The combination of appropriate differentiation protocols and cell culture polymeric biomaterials for the differentiation of hPSCs into specific cell lineages will produce a large quantity of highly pure GMP-grade differentiated cells for use in translational medicine

Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not

The combined influence of substrate elasticity and surface-grafted molecules on the exvivo expansion of hematopoietic stem and progenitor cells

Umbilical cord blood (UCB) is an attractive source of hematopoietic stem and progenitor cells (HSPCs) for transplantation. However, the low number of HSPCs from a single UCB donor limits the direct transplantation of UCB to patients. Because little is known about the effects of the physical microenvironment on HSPC expansion, we investigated the exvivo expansion of HSPCs cultured on biomaterials with different elasticities and grafted with different nanosegments. Polyvinylalcohol-co-itaconic acid (PVA-IA)-coated dishes with different stiffnesses ranging from a 3.7kPa to 30.4kPa storage modulus were used. Fibronectin or an oligopeptide (CS1, EILDVPST) was grafted onto the PVA-IA substrates. High exvivo fold expansion of HSPCs was observed in the PVA-IA dishes grafted with fibronectin or CS1, which displayed an intermediate stiffness ranging from 12.2kPa to 30.4kPa. The fold expansion was more than 1.4 times higher than that cultured in tissue culture polystyrene dishes (TCPS, 12GPa). Furthermore, HSPCs cultured in fibronectin or CS1-grafted PVA-IA-coated dishes with a stiffness of 12.2-30.4kPa generated more pluripotent colony-forming units (CFU-GM and CFU-GEMM) than those in TCPS dishes. This result indicates that both the physical and biological properties of biomaterials affect the exvivo expansion of HSPCs

Stem cell culture on polyvinyl alcohol hydrogels having different elasticity and immobilized with ECM-derived oligopeptides

The physical characteristics of cell culture materials, such as their elasticity, affect stem cell fate with respect to cell proliferation and differentiation. We systematically investigated the morphologies and characteristics of several stem cell types, including human amniotic-derived stem cells, human hematopoietic stem cells, human induced pluripotent stem (iPS) cells, and embryonic stem (ES) cells on poly(vinyl alcohol) (PVA) hydrogels immobilized with and without extracellular matrix-derived oligopeptide. Human ES cells did not adhere well to soft PVA hydrogels immobilized with oligovitronectin, whereas they did adhere well to PVA hydrogel dishes with elasticities greater than 15 kPa. These results indicate that biomaterials such as PVA hydrogels should be designed to possess minimum elasticity to facilitate human ES cell attachment. PVA hydrogels immobilized with and without extracellular matrix-derived oligopeptides are excellent candidates of cell culture biomaterials for investigations into how cell culture biomaterial elasticity affects stem cell culture and differentiation