1.Analysis of non-tumor diseases affecting the diagnosis and treatment of cancer patients
Sen HAN ; Wei LI ; Jian FANG ; Jun NIE ; Ling DAI ; Weiheng HU ; Xiaoling CHEN ; Jie ZHANG ; Xiangjuan MA ; Guangmin TIAN ; Di WU ; Jieran LONG ; Jindi HAN ; Yang WANG ; Ziran ZHANG ; Weiping LIU ; Jun ZHU
Chinese Journal of Clinical Oncology 2018;45(10):517-520
Objective:To investigate the types of non-tumor diseases in patients with cancer, and to explore the effects of those dis-eases on the diagnosis and treatment of cancer patients. Methods:We collected the medical records of cancer patients from January 2013 to December 2017 in Peking University Cancer Hospital, and screened for non-tumor diseases. The clinical records of the patients in this group were analyzed retrospectively, and the effects of those diseases on the diagnosis and treatment of tumors were dis-cussed. Results:Of the 1,323 cases of inter-hospital consultation, 1,153 cases of non-tumor disease (87.2%) were selected. There were 773 men (67.0%) and 380 women (33.0%) included. The median age was 62 (14-90) years. The primary tumor types included lung can-cer, gastric cancer, lymphoma, colorectal cancer, esophageal cancer, breast cancer, malignant melanoma, liver cancer, cholangiocarci-noma/gallbladder cancer, pancreatic cancer, and other tumors. Non-neoplastic diseases included cardiovascular disease in 356 cases (30.9%), respiratory system disease (17.0%) in 196 cases, digestive system disease in 107 cases (9.3%), skin and venereal diseases in 81 cases (7.0%), nervous system lesions (6.4%) in 74 cases, urinary system disease in 72 cases (6.2%), blood disease in 70 cases (6.1%), en-docrine and metabolic diseases in 47 cases (4.1%), autoimmune disease in 23 cases (2.0%), and other diseases (11.0%) in 127 cases. Impact on tumor diagnosis and treatment was as follows:direct, 771 cases (66.9%);no influence, 313 cases (27.1%);and uncertain, 69 cases (6.0%). Conclusions:Cardiovascular disease is a major non-tumor disease associated with cancer. Non-neoplastic diseases are important factors affecting the diagnosis and treatment plans of cancer.
2.Differentiation of adipose-derived stem cells toward nucleus pulposus-like cells induced by hypoxia and a three-dimensional chitosan-alginate gel scaffold in vitro.
Zhicheng ZHANG ; Fang LI ; Haiquan TIAN ; Kai GUAN ; Guangmin ZHAO ; Jianlin SHAN ; Dajiang REN
Chinese Medical Journal 2014;127(2):314-321
BACKGROUNDInjectable three-dimensional (3D) scaffolds have the advantages of fluidity and moldability to fill irregular-shaped defects, simple incorporation of bioactive factors, and limited surgical invasiveness. Adipose-derived stem cells (ADSCs) are multipotent and can be differentiated toward nucleus pulposus (NP)-like cells. A hypoxic environment may be important for differentiation to NP-like cells because the intervertebral disc is an avascular tissue. Hence, we investigated the induction effects of hypoxia and an injectable 3D chitosan-alginate (C/A) gel scaffold on ADSCs.
METHODSThe C/A gel scaffold consisted of medical-grade chitosan and alginate. Gel porosity was calculated by liquid displacement method. Pore microstructure was analyzed by light and scanning electron microscopy. ADSCs were isolated and cultured by conventional methods. Passage 2 BrdU-labeled ADSCs were co-cultured with the C/A gel. ADSCs were divided into three groups (control, normoxia-induced, and hypoxia-induced groups). In the control group, cells were cultured in 10% FBS/DMEM. Hypoxia-induced and normoxia-induced groups were induced by adding transforming growth factor-β1, dexamethasone, vitamin C, sodium pyruvate, proline, bone morphogenetic protein-7, and 1% ITS-plus to the culture medium and maintaining in 2% and 20% O2, respectively. Histological and morphological changes were observed by light and electron microscopy. ADSCs were characterized by flow cytometry. Cell viability was investigated by BrdU incorporation. Proteoglycan and type II collagen were measured by safranin O staining and the Sircol method, respectively. mRNA expression of hypoxia-inducing factor-1α (HIF-1α), aggrecan, and Type II collagen was determined by reverse transcription-polymerase chain reaction.
RESULTSC/A gels had porous exterior surfaces with 80.57% porosity and 50-200 üm pore size. Flow cytometric analysis of passage 2 rabbit ADSCs showed high CD90 expression, while CD45 expression was very low. The morphology of induced ADSCs resembled that of NP cells. BrdU immunofluorescence showed that most ADSCs survived and proliferated in the C/A gel scaffold. Scanning electron microscopy showed that ADSCs grew well in the C/A gel scaffold. ADSCs in the C/A gel scaffold were positive for safranin O staining. Hypoxia-induced and normoxia-induced groups produced more proteoglycan and Type II collagen than the control group (P < 0.05). Proteoglycan and Type II collagen levels in the hypoxia-induced group were higher than those in the normoxia-induced group (P < 0.05). Compared with the control group, higher mRNA expression of HIF-1α, aggrecan, and Type II collagen was detected in hypoxia-induced and normoxiainduced groups (P < 0.05). Expression of these genes in the hypoxia-induced group was significantly higher than that in the normoxia-induced group (P < 0.05).
CONCLUSIONADSCs grow well in C/A gel scaffolds and differentiate toward NP-like cells that produce the same extracellular matrix as that of NP cells under certain induction conditions, which is promoted in a hypoxic state.
Adipose Tissue ; cytology ; Alginates ; chemistry ; Animals ; Cell Differentiation ; physiology ; Cells, Cultured ; Chitosan ; chemistry ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Rabbits ; Stem Cells ; cytology ; physiology ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry