Chemotherapy has long been considered as one of useful strategies for cancer treatment. It is primarily based on the apoptosis that can selectively kill cancer cells. However, cancer cells can progressively develop an acquired resistance to apoptotic cell death, rendering refractory to chemo- and radiotherapies. Although the mechanism by which cells attained resistance to drug remains to be clarified, it might be caused by either pumping out of them or interfering with apoptotic signal cascades in response to cancer drugs. In case that cancer cells are defective in some part of apoptotic machinery by repeated exposure to anticancer drugs, alternative cell death mechanistically distinct from apoptosis could be adopted to remove cancer cells refractory to apoptosis-inducing agents. This review will mainly deal with harnessing of necrotic cell death, specifically, programmed necrosis and practical uses. Here, we begin with various defects of apoptotic death machinery in cancer cells, and then provide new perspective on programmed necrosis as an alternative anticancer approach.
Apoptosis ; Autophagy ; Cell Death ; Drug Therapy ; Necrosis* ; Radiotherapy

No abstract available.
Drug Therapy, Combination* ; Necrosis* ; Radiotherapy* ; Small Cell Lung Carcinoma*

PURPOSE: The current study was designed to evaluate the ability of thallium-201 scintigraphy to predict the response to preoperative chemotherapy in osteosarcoma, by comparing changes in thallium uptake ratio after chemotherapy to the tumor necrosis ratio. MATERIALS AND METHODS: Twelve osteosarcoma patients were included in this study. Thallium-201 scintigraphy was performed before and after preoperative chemotherapy, and the degree of tumor necrosis was estimated by histologic mapping postoperatively. To quantitatively determine thallium uptake, we drew a region of interest on the tumor side and on the contralateral normal side as a mirror image, and calculated the uptake ratio with dividing the gamma count in the tumor side by that of the normal side. We calculated these percent changes of thallium uptake ratio in the early and delayed phases, and compared these to the corresponding tumor necrosis ratio. RESULTS: Percent changes in the thallium uptake ratio were found to be correlated with the tumor necrosis ratio (p<0.03). This correlation was found in both the early (p<0.03) and delayed phase (p<0.03); moreover the correlation coefficient in early phase (0.79) was greater than that in the delayed phase (0.67). CONCLUSION: Thallium-201 scintigraphy could be effective at predicting the response to preoperative chemotherapy in osteosarcoma.
Drug Therapy* ; Humans ; Necrosis ; Osteosarcoma* ; Radionuclide Imaging* ; Thallium

Humans ; Mucocutaneous Lymph Node Syndrome ; drug therapy ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; Tumor Necrosis Factors

Evidence has indicated that low doses of anti-tumor regimens can induce cell apoptosis in vitro, although different regimens induce apoptosis by different mechanism and pathway. In recent years, new tumor treatment strategy has been mainly focused on inducing tumor cell apoptosis. The present review discusses the advantages and disadvantages of inducing tumor cell apoptosis. The benefit of inducing apoptosis is not to cause inflammatory reaction, but as its disadvantage, it inhibits immune responses, and the phagocytosis of apopotic bodies may result in horizontal transfer of genes (including oncogenes and other oncogenic materials), which can be one of the causes of tumor relapse. This paper proposes that the tumor treatment strategy should be turn into promoting tumor cell necrosis and inducing anti-tumor immune responses.
Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Necrosis ; chemically induced ; Neoplasms ; drug therapy ; immunology ; pathology

Avascular necrosis is a progressively devastating disease and primarily affects weight-bearing joints. The hip is the most commonly affected joint. In early stage, nonoperative (including pharmacologic intervention and biophysical treatments) and operative modalities for protecting hip joint have become the main therapeutic methods. However there is still no satisfied mothod with reasonable effect. According to the treatment of the avascular necrosis of the femoral head of the pre-collapse stage, core decompression with modification of technique is still one of the safest and most commonly employed procedures. Recently there have been attempts to enhance the effect of core decompression with use of various growth and differentiation factors. Which is the hot spot of current research. Early diagnosis is the key to the treatment of the avascular necrosis of the femoral head. Comprehensive treatment which is based on the core decompression is still the main treatment of today.
Biophysical Phenomena ; Femur Head Necrosis ; drug therapy ; physiopathology ; surgery ; therapy ; Humans ; Weight-Bearing

Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.
Antineoplastic Agents/therapeutic use* ; Apoptosis ; Autophagy/physiology* ; Humans ; Necrosis/drug therapy* ; Neoplasms/therapy*

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

The ethyl acetate fraction of ethanol extract of Eucommiae Cortex can effectively inhibit joint inflammation and bone destruction in rats with collagen-induced arthritis(CIA) and has a potential therapeutic effect on rheumatoid arthritis. The triterpenoid(EU-Tid) and iridoid(EU-Idd) of Eucommiae Cortex are derivatives isolated from the ethyl acetate fraction of the ethanol extract of Eucommiae Cortex, and it is not clear whether they have inhibitory effects on joint inflammation and bone erosion in CIA rats. Therefore, based on the CIA model, the effects of EU-Tid, EU-Idd, and their combination(EU-TP) on arthritis in rats were observed, and the material basis of Eucommiae Cortex against arthritis was further clarified. The samples were collected two and four weeks after administration to observe the pathological changes in different stages of arthritis in CIA rats. For the rats in the model control group, with the prolongation of the disease course, the paw volume and arthritis score increased and histopathological lesions aggravated. Compared with the model control group, the drug administration groups showed reduced paw volumes and arthritis scores, and improved joint lesions and cartilage destruction. Additionally, the mRNA expression levels of tumor necrosis factor-α(TNF-α), interleukin-17(IL-17), and interleukin-23(IL-23) in the spleen were down-regulated in the drug administration groups. EU-TP and EU-Tid at concentrations of 160 and 320 μg·mL~(-1) could significantly inhibit the proliferation of human fibroblast-like synoviocytes-RA(HFLS-RA) and nitric oxide(NO) release in the supernatant of RAW264.7 cells induced by lipopolysaccharide(LPS) at the concentration range of 10-80 μg·mL~(-1) in vitro. EU-Idd had no effect on the proliferation of HFLS-RA but could reduce the NO release at concentrations of 40 and 80 μg·mL~(-1). The results indicated that the terpenoids of Eucommiae Cortex had great potential in the treatment of rheumatoid arthritis.
Rats ; Humans ; Animals ; Arthritis, Experimental/drug therapy* ; Iridoids/pharmacology* ; Triterpenes/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Tumor Necrosis Factor-alpha ; Plant Extracts/pharmacology* ; Inflammation/drug therapy* ; Ethanol ; Cytokines

PURPOSE: Anthracycline induced cardiotoxicity is well known and its pathology is characterized by localized myocardial cell necrosis and myocardial fibrosis. The variability in QT interval duration amongst the different leads of the standard 12-lead ECG(QT dispersion) is considered to reflect inhomogenous repolarization of the myocardium. The aim of this study was to assess the effects of anthracycline on cardiac electrophysiology, with special emphasis on dispersion of QT interval and its relation to cumulative doses. METHODS: Heart rate-corrected QT interval(QTc) and QT dispersion(QTd) were measured in standard 12-lead ECG in 34 cancer patients and compared with those of normal control. RESULTS: QTc was increased in cancer patients(462.2+/-36.0 msec vs 447.0+/-19.7 msec) but QTd was not different between the cancer patients and normal control as a whole(40.8+/-12.5 msec vs 36.6+/-9.2 msec). But in the 5-10 year age group, QTd was increased in cancer patients in comparison with that of age matched control(44.1+/-14.8 msec vs 34.0+/-9.7 msec). Also QTc in the 5-10 year age group, but not in the 11-15 year age group, was increased in cancer patients in comparison with that of age matched control(478.0+/-40.8 msec vs 446.5+/-20.9 msec). QTc and QTd were not different according to the cumulative doses of anthracycline in the cancer patients. Left ventricular systolic function was found normal in all cancer patients by echocardiographic examination. CONCLUSION: In the absence of a significant modification of echocardiographic parameters, increased inhomogeneity of ventricular repolarization could be an early marker of anthracycline cardiotoxicity. The changes of repolarization parameters were significant only in the younger age group and were not significant according to the cumulative doses. Anthracycline seemed to induce cardiotoxity from the small dose and more significantly in the younger heart.
Anthracyclines* ; Cardiac Electrophysiology ; Child* ; Drug Therapy* ; Echocardiography ; Electrocardiography ; Fibrosis ; Heart ; Humans ; Myocardium ; Necrosis ; Pathology