STAMBP is Required for Long-Term Maintenance of Neural Progenitor Cells Derived from hESCs.

Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc. Previous biochemical investigations and loss-of-function studies in mice have provided insights into the mechanism of STAMBP, however, it remains controversial how STAMBP deficiency leads to malformation of those affected tissues in patients. In this study, we investigated the function and underlying mechanism of STAMBP during neural differentiation of human embryonic stem cells (hESCs). We found that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STAMBP-deficiency. Our study not only provides novel insight into the mechanism of neural defects in STAMBP mutant patients, it also indicates that the death receptor mediated apoptosis is an obstacle for long-term maintenance/expansion of NPCs in vitro thus counteracting this cell death pathway could be beneficial to the generation of NPCs in vitro.

Medical cost of environmental pollution: evidence from the Chinese Social Survey.

Environmental pollution impairs residents' health, while the pursuit of health is highly correlated to medical costs. Understanding how environmental pollution affects medical costs is closely linked to the welfare of society. Based on theoretical analysis, this paper uses data from 5112 households of the Chinese Social Survey (CSS) in 2019, constructs a composite indicator to quantify environmental pollution using respondents' evaluations, and empirically investigates the causal effect of environmental pollution on household medical cost and the mechanism. The conclusions are shown as follows. First, environmental pollution can increase household medical costs, and this estimation result still holds after dealing with the endogeneity problem and other robustness tests. Second, there is heterogeneity in the impact of environmental pollution on household medical costs, households in the upper socioeconomic class, with heavy pension burdens or with strong health insurance coverage are more sensitive to environmental pollution and incur relatively higher household medical costs. Third, environmental pollution reduces residents' satisfaction with their spiritual life, which adversely affects their physical and mental health and can increase household medical costs. Residents' satisfaction with their spiritual life is an important mechanism for environmental pollution to affect household health care expenditures. Therefore, governments should enhance the enforcement of environmental protection and governance, strengthen the awareness of green issues and health education, and increase the supply of facilities for leisure and sports, thus reducing medical costs due to environmental pollution and easing the medical burden of residents.

Effects of air pollution on cardiovascular health in patients with type 2 diabetes mellitus: Evidence from a large tertiary hospital in Shandong Province, China.

Air pollution has posed serious threats to human health. Based on the microdata of a large tertiary hospital in Shandong Province from 2016 to 2021, combined with the macro data such as air quality monitoring data, meteorological data, and city-level regional socio-economic data, this paper empirically tests the impact of air pollution instrumented by thermal inversions on the cardiovascular health of patients with type 2 diabetes mellitus (T2DM) and its group differences. The results show that: (1) Air pollution has a negative impact on the cardiovascular health of patients with T2DM, that is, the cardiovascular health of patients with T2DM will decline in regions with high air pollution; (2) The impact of air pollution on cardiovascular health in T2DM patients is heterogeneous, with males and older patients bearing greater air pollution health losses; (3) From the perspective of the external environment, the negative effects of environmental pollution on patients' health were significantly reduced in areas with higher environmental regulation intensity and better public health conditions, indicating the necessity of strengthening environmental governance and increasing public health expenditure.

3D localization based on anatomical LANDmarks in the treatment of pulmonary nodules.

Background: Various methods exist for locating lung nodules, each with its own advantages and disadvantages. Aiming to find a more accurate, safe, effective, economical and practical method for locating lung nodules, this study evaluated the safety and feasibility of a precise three-dimensional (3D) method for positioning small pulmonary nodules based on anatomical landmarks. Methods: From June 2019 to December 2021, 120 patients with 131 pulmonary nodules who underwent video-assisted thoracoscopic surgery at the University of Hong Kong-Shenzhen Hospital were included in the study. Surgical data such as the positioning time, accuracy rate, pathological result, localization-related complication rate and length of postoperative hospital stay were retrospectively reviewed and analyzed. During surgery, pulmonary nodules were accurately located by the 3D positioning method based on anatomical landmarks and then removed to determine the pathology. Results: A total of 120 patients, including 35 males and 85 females, were included, and the median age was 53 years [interquartile range (IQR), 41-63 years]. No mortality or major morbidity occurred within 30 days. The median localization time was 11 minutes (IQR, 8-14 minutes). The accuracy of localization was 98.5%. The median diameter of the pulmonary nodules was 8 mm (IQR, 7-13 mm), and the median distance from the visceral pleura was 6 mm (IQR, 2-10 mm). No location-related complications occurred. The median length of postoperative hospital stay was 5 days (IQR, 3-7 days). Conclusions: The proposed positioning method is accurate, safe and feasible for selected patients with pulmonary nodules. Compared with other preoperative and intraoperative positioning methods, it can significantly reduce localization-related complications.

Spontaneous ventilation anesthesia combined with uniportal and tubeless thoracoscopic sympathectomy in selected patients with primary palmar hyperhidrosis.

BACKGROUND: To assess the feasibility and safety of tubeless video-assisted thoracoscopic sympathectomy (VATS) with a single 5 mm port under nonintubated, intravenous anesthesia with spontaneous ventilation in selected patients with primary palmar hyperhidrosis (PPH). METHODS: Adults (aged between 18 and 60 years) with moderate or severe PPH symptoms were enrolled. Demographic information and clinical data were obtained from 172 consecutive patients undergoing thoracoscopic surgery for PPH from March 2014 to December 2020. The primary outcomes were the rate of complications, including death, and the intraoperative conversion rate to 3-port VATS. The secondary outcomes were the conversion rate to intubated anesthesia during the operation and the surgical duration and pain score of postoperative day 0. RESULTS: In total, 172 patients were included with 88 males and 84 females. The median age was was 25 years (IQR:21-30 years). No mortalities or major morbidities occurred in any patient. The overall median surgical duration was 53 min (IQR:37-72 min). The median length of postoperative hospital stay was one day (IQR:one-one day). The median pain score of POD0 was 2 (IQR:2-2). Intraoperative conversion to 3-port VATS followed by drainage tube insertion occurred in one (0.6%) patient due to extensive pleural adhesions. No patients required conversion to intubated anesthesia during surgery. No postoperative mechanical ventilation was noted in any patient. CONCLUSIONS: For selected patients with PPH, tubeless VATS with a single 5 mm port using spontaneous ventilation anesthesia can be considered a feasible and safe operation. The surgical wound is extremely small and the operation time is shorter than the conventional technique. Trial registration This study was in conformity with the Declaration of Helsinki, and was approved by the National Ethics Committee of the University of the Hong Kong-Shenzhen Hospital (Approval number: [2020]70). We registered the study in the Chinese Clinical Trial Registry (Registration number: ChiCTR2100049063) in 2021.Informed consent was collected from all the participants of this study. URL for this clinical trial registration is: https://www.chictr.org.cn/index.aspx .

Ruthenium Complexes as Promising Candidates against Lung Cancer.

Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.

Superior mesenteric artery syndrome after lung transplantation: a rare early gastrointestinal complication of lung transplantation.

Gastrointestinal complications sometimes occur after lung transplantation and remain a cause of postoperative morbidity. Superior mesenteric artery syndrome is caused by the compression of the duodenum by the superior mesenteric artery, but few reports have described superior mesenteric artery syndrome after lung transplantation. We herein report two cases of superior mesenteric artery syndrome as an early complication after lung transplantation. Both patients were emaciated and had lost weight before transplantation. They also lost an additional 2-4 kg early after transplantation. They were medically treated with enteral nutrition and recovered without recurrence of the syndrome. Since critically ill patients with pulmonary disease usually lose weight both before and early after lung transplantation, superior mesenteric artery syndrome is important to consider in the differential diagnosis of gastrointestinal complications after transplantation.

Localizing small lung lesions in video-assisted thoracoscopic surgery via radiofrequency identification marking.

BACKGROUND: To facilitate accurate localization of small lung lesions in thoracoscopic surgery, we employed a micro-radiofrequency identification tag designed to be delivered through the 2-mm working channel of a flexible bronchoscope. This report presents the results of preclinical studies of our novel localizing technique in a canine model. METHODS: To evaluate functional placement, three types of tags [Group A, tag alone (n = 18); Group B, tag + resin anchor (n = 15); and Group C, tag + NiTi coil anchor (n = 15)] were bronchoscopically placed in subpleural areas and subsegmental bronchi via our new delivery device; tags were examined radiographically on days 0-7 and day 14. In addition, eight tags, which were placed at a mean depth of 13.3 mm (range 9-15.7 mm) from visceral pleura in bronchi with a mean diameter of 1.46 mm (range 0.9-2.3 mm), were recovered by partial lung resection under video-assisted thoracoscopic surgery using a 13.56-MHz wand-shaped probe with a 30-mm communication range. RESULTS: Peripheral airway placement: Group C had a significantly higher retention rate than the other two groups (retention rate at day 14: Group A, 11.1 %; Group B, 26.7 %; Group C, 100.0 %; P < 0.0001). Central airway placement: Overall retention rate was 73.3 % in Group C, and placement was possible in bronchi of up to 3.3 mm in diameter. Outcomes of partial resection: Tag recovery rate was 100 %, mean time required for tag detection was 10.8 s (range 8-15 s), and mean surgical margin from the delivered tag was 9.13 mm (range 6-13 mm). CONCLUSION: Radiofrequency identification marking enabled accurate localization with depth, which could ensure effective deep resection margins.

Effects of atorvastatin combined with low-molecular-weight heparin on plasma inflammatory cytokine level and pulmonary pathophysiology of rats with sepsis.

The aim of the present study was to investigate the effect of atorvastatin combined with low-molecular-weight heparin (LMWH) on plasma early inflammatory cytokine levels as well as pulmonary pathophysiology of rats with sepsis. A total of 122 rats were randomly divided into five groups including the sham operation group (n=10), CLP group (n=10), atorvastatin group (n=34, 20 mg/kg/day), LMWH group (n=34, 100 IU/kg/day), and atorvastatin combined with LMWH group (n=34). Blood samples from 6 rats in each group were collected to detect TNF-α, IL-1ß and HMGB1 concentration in plasma by linked immunosorbent assay at baseline and postoperatively at 4, 8, 12 and 24 h. Pulmonary pathophysiology was observed postoperatively at 24 h. The remaining 10 rats in each group were used to calculate the 7-day cumulative mortality rate. Compared to the sham operation group, the scores in CLP were greater than those of the sham operation group (P<0.05). Compared to the CLP group, the sepsis severity scores of the atorvastatin, LMWH, and atorvastatin combined with LMWH groups decreased gradually. Significant difference was detected in the four groups (P<0.05 0.01). Compared to the sham operation group, at 4, 8, 12 and 24 h, the TNF-α, IL-1ß and HMGB1 levels in plasma in CLP increased significantly (P<0.01). Compared to the CLP group, the TNF-α, IL-1ß and HMGB1 levels of plasma in other groups decreased gradually, and there was a significant difference in the four groups (P<0.01). At 24 h post operation, compared to the sham operation group, the damage of pulmonary pathophysiology in CLP was more severe. Compared to the CLP group, the damage of pulmonary pathophysiology in other groups was slight. Compared to the CLP group, the 7-day cumulative mortality rate in other groups decreased significantly (P<0.05). In conclusion, atorvastatin, combined with LMWH can decrease sepsis severity, plasma inflammatory cytokine levels, pulmonary pathophysiology, and the 7-day cumulative mortality rate. Atorvastatin, and LMWH may therefore be useful for the treatment of sepsis due to its ability to inhibit the release of TNF-α, IL-1ß and HMGB1 in septic rats.

Imatinib for sclerodermatous graft-versus-host disease in lung transplantation.

Imatinib has been proposed as a treatment for sclerodermatous chronic graft-versus-host disease (GVHD) due to its antifibrotic activity. Because imatinib has a potentially adverse effect on wound healing, the safety of its perioperative use in lung transplantation is unknown. Herein, we present a patient who underwent bilateral living-donor lobar lung transplantation for pulmonary complications after bone marrow transplantation, who had also received treatment with imatinib for sclerodermatous GVHD. Imatinib was discontinued 3 weeks before lung transplantation, but was resumed 1 week postoperatively for an exacerbation of sclerodermatous GVHD. Seven months after the postoperative the patient continues to do well without complications.

Thoracoscopic bronchoplasty using continuous sutures in complete monitor view.

Thoracoscopic sleeve lobectomy in a complete monitor view is rarely reported. In thoracoscopic bronchoplasty, the insertion of a needle to the optimal point at the appropriate angle is difficult because of the restricted movement, and the limitation of monitor visualization complicates the creation of extraluminal ligations for anastomosis of the deep part of the bronchus. We report a case of sleeve resection of the right upper lobe with continuous sutures in a complete monitor view. Anastomosis with continuous sutures, which requires only three knots, is thought to be useful for bronchoplasty in thoracoscopic surgical procedures.

Right lower lobe sleeve resection: bronchial flap to correct caliber disparity.

Sleeve resection of the right lower lobe is performed infrequently. Caliber disparity between the truncus intermedius and the middle lobe bronchus is a major problem. We report a case of lung cancer completely resected by sleeve resection of the right lower lobe. A bronchial flap constructed from the distal bronchial end was used for correction of the caliber disparity, and interlobar dissection between the upper and middle lobes effectively reduced the tension on the anastomotic site. These procedures are useful for sleeve resection of the right lower lobe.

Post-ischemic infusion of atrial natriuretic peptide attenuates warm ischemia-reperfusion injury in rat lung.

BACKGROUND: The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung during ischemia. In this study we investigated the effect on lung ischemia-reperfusion injury of administering synthetic ANP (carperitide) at the onset of reperfusion after warm ischemia. METHODS: An isolated rat lung perfusion model was used. The rats were allocated into three groups: the control group; the ANP group; and the sham group. In the control and ANP groups, the heart-lung block was exposed to 60 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. At the onset of reperfusion, either saline or ANP was added to the perfusate. In the sham group, lungs were continuously perfused without ischemia and only saline was added to the perfusate. RESULTS: ANP significantly reduced pulmonary vascular resistance and pulmonary edema, and improved oxygenation. It also significantly increased cGMP levels in reperfused lungs. Histologically, lungs in the ANP group showed significantly fewer signs of injury and fewer cells demonstrated apoptotic changes or single-stranded DNA than lungs in the control group. CONCLUSIONS: Our results indicate that ANP administered at the onset of reperfusion increases cGMP in lung tissue and attenuates warm ischemia-reperfusion injury in isolated perfused rat lung.

Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs.

BACKGROUND: Thioredoxin is a ubiquitous protein with anti-oxidative, anti-apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T, Yokomise H et al. Attenuation of ischaemia reperfusion injury by human thioredoxin. Thorax 1995; 50: 387-391] that rhTRX protected lungs from ischemia-reperfusion injury as a radical scavenger; however, the mechanism was not elucidated. Therefore, we investigated the effect of perfusion and inhalation of rhTRX, and the associated mechanisms, by analyzing the concentrations and molecular states of the perfused rhTRX. MATERIALS AND METHODS: Perfusion and inhalation studies of rhTRX were conducted with an isolated rat-lung perfusion model. The heart-lung block was perfused for 15 min and subsequently exposed to a 55-min ischemia followed by a 120-min reperfusion. Pulmonary artery pressure, weight gain, dynamic airway resistance, pulmonary compliance, and tidal volume were measured continuously. The concentrations and molecular states of the perfused rhTRX were measured. RESULTS: A 350-microg/ml perfusion of rhTRX decreased post-ischemic pulmonary artery pressure (P < 0.05), while a 200-microg/ml perfusion did not. Throughout the experiment, the rhTRX concentrations were constant, and the rhTRX molecules were mostly dimeric. The inhalation of rhTRX showed adverse effects on the pulmonary function compared with the control group (P < 0.05). CONCLUSIONS: A 350-microg/ml perfusion, but not inhalation, of rhTRX protected rat lungs from ischemia-reperfusion injury. rhTRX was effective in dimeric form without transit to the lung tissue. rhTRX may be effective by some mechanism other than radical scavenging.

Nebulized phosphodiesterase III inhibitor during warm ischemia attenuates pulmonary ischemia-reperfusion injury.

BACKGROUND: The control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle. We hypothesized that nebulized milrinone would mitigate warm ischemia-reperfusion injury of lung. METHODS: This study was conducted with an isolated rat lung perfusion model. Lungs were excised, exposed to 55-minute ischemia at 37 degrees C, and reperfused for 60 minutes. During ischemia, nebulized milrinone (n = 6) or saline (n = 6) was inhaled. Lungs were continuously perfused without ischemia as a sham group (n = 6). Airway resistance, pulmonary vascular resistance, pulmonary compliance, weight gain and blood gas were measured. Adenine nucleotide levels and apoptosis were investigated in the reperfused lungs. RESULTS: Milrinone nebulization decreased post-ischemic pulmonary vascular resistance (0.98 +/- 0.05 and 1.74 +/- 0.17 cm H(2)O/ml.min at 60 minutes of reperfusion in the milrinone and control groups, respectively [p < 0.01]). It did not alter cyclic adenosine monophosphate levels, but it did elevate adenosine triphosphate levels (9.87 +/- 0.38 and 6.91 +/- 0.45 in the milrinone and control groups, respectively [p < 0.01]) and suppressed apoptosis (3.83 +/- 0.91 and 46.17 +/- 3.39 of mean apoptotic cell numbers in the milrinone and control groups, respectively [p < 0.01]). CONCLUSIONS: Milrinone nebulization decreased post-ischemic pulmonary vascular resistance, elevated adenosine triphosphate levels, and suppressed apoptosis. Nebulized milrinone has some protective effects against warm ischemia.

Successful sub-zero non-freezing preservation of rat lungs at -2 degrees C utilizing a new supercooling technology.

BACKGROUND: A lower temperature, namely below 0 degrees C, has been thought to be desirable for organ preservation because of the lower rate of metabolism; however, its benefits are still poorly understood. Supercooling is a non-freezing state of liquid below the freezing point, and the new development of a refrigerator for supercooling has now made it possible to preserve organs at sub-zero temperatures in a non-frozen state without cryoprotectants. METHODS: Rat lungs were ventilated and perfused for 60 minutes in the 3 groups (n = 7 each): (1) the fresh group, in which the lungs were reperfused immediately after harvesting; (2) the 4 degrees C group, in which the lungs were stored after harvesting in ET-Kyoto solution at 4 degrees C for 17 hours before reperfusion; and (3) the supercooling group, in which lungs were preserved in ET-Kyoto solution at -2 degrees C for 17 hours. RESULTS: Ischemia-reperfusion injury was significantly attenuated in the supercooling group, with a decrease in the pulmonary artery pressure (p < 0.02) and weight gain (p < 0.001), and an increase in the tidal volume (p = 0.001) and arterial oxygen tension (p < 0.001) compared with the 4 degrees C group. In the supercooling group, most of these indicators were equivalent to the fresh lung, with less damage to the endothelial cells of the pulmonary arteries and higher levels of adenosine triphosphate than in the 4 degrees C group. CONCLUSIONS: Lungs stored using this new supercooling method of lung preservation showed better organ function than conventional storage at 4 degrees C.

Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs.

BACKGROUND: Non-heart-beating donors are expected to ameliorate shortages of donors for organ transplantation. The issue of preventing warm ischemic injury after circulatory arrest must be investigated. In the current study, we investigated whether isoflurane inhalation during warm ischemia could attenuate ischemia reperfusion injury (IRI) of the lung. METHODS: An isolated perfused rat lung model was used. The rats were allocated into four groups: the no ischemia group; the ischemia-1 minimum alveolar concentration (MAC) iso group (ventilation with air and 1.38% isoflurane); the Ischemia-3MAC iso group (ventilation with air and 4.2% isoflurane); and the Ischemia-no treatment group (ventilation with only air). Lungs were subjected to 50 min of ischemia at 37 degrees C. Physiological lung functions were measured after reperfusion in experiment one. Mitochondrial control ratio (RCR), cytochrome-c release from mitochondria, and caspase activities just after warm ischemia were measured in experiment two. RESULTS: Pulmonary functions in the Ischemia-1MAC iso group were significantly greater than those in the Ischemia-no treatment group for experiment one. There were no dose-dependent effects between 1MAC and 3MAC isoflurane. In experiment two, RCR in the Ischemia-1MAC iso group was significantly greater than that in the Ischemia-no treatment group. Cytochrome-c release and caspase-9 activity in the Ischemia-1MAC iso group were significantly decreased compared to those in the Ischemia-no treatment group. CONCLUSIONS: Isoflurane inhalation attenuates warm IRI with the protection of mitochondria. Our results suggest that isoflurane inhalation after circulatory arrest can be a simple and effective method to protect the lung against warm ischemia.

Protective effect of a nebulized beta2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs.

BACKGROUND: It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta2-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm ischemia would increase lung tissue cyclic adenosine monophosphate (cAMP) levels, resulting in lung protection. METHODS: Two studies were conducted. The first investigated the effect of SLM nebulization during ischemia on pulmonary ischemia-reperfusion injury, using an isolated rat lung-perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. Several parameters were measured during reperfusion. In the second study, to measure changes in lung tissue cAMP levels during warm ischemia with or without SLM nebulization, rat lungs were harvested and exposed to 60 minutes of warm ischemia with ventilation. RESULTS: Salmeterol xinafoate nebulization significantly decreased the pulmonary shunt fraction, airway resistance, and pulmonary vascular resistance. It also inhibited pulmonary edema throughout the reperfusion period. Lung tissue cAMP was effectively maintained by SLM nebulization at the end of reperfusion. Myeloperoxidase activity in the lungs was decreased significantly by SLM nebulization. Lung tissue cAMP levels decreased during the 60 minutes of warm ischemia, but increased with SLM nebulization (p < 0.01). CONCLUSIONS: Our results confirmed that SLM nebulization during warm ischemia maintained lung tissue cAMP levels, resulting in the alleviation of pulmonary warm ischemia-reperfusion injury.

Strategies to endow cytotoxic T lymphocytes or natural killer cells with antibody activity against carcinoembryonic antigen.

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are main effecter cells in cellular immunity against tumor cells. T-cell immunotherapy is based on the assumption that tumor(-associated) antigen (TA) peptides are correctly presented by HLA class I molecules on target tumor cells, and NK cell immunotherapy is based on the hypothesis that cell surface TAs or ligands for NK receptors are widely expressed in tumor cells. However, human tumor cells often lose HLA class I molecules, and target cell ligands for NK receptors are not always expressed in human tumor cells. These altered HLA class I phenotypes and non-ubiquitous expression of NK receptor ligands constitute the major tumor escape mechanism facing tumor-specific CTL and/or NK cell mediated responses. These facts also indicate that it is not easy to eliminate the target tumors only by activating tumor-specific CTLs or NK cells with cancer vaccine treatments. On the other hand, it is easily confirmed by immunohistochemistry whether or not antibody-recognized TAs exist on the cell surface of target tumor cells. Therefore, endowing CTLs or NK cells with antigen-binding specificity of anti-TA antibody is a promising approach for re-targeting the activities of these effector cells to tumor cells in an HLA-independent manner. This review summarizes the following four new strategies for re-targeting CTLs or NK cells to carcinoembryonic-antigen-expressing tumor cells: (1) bispecific antibody technology; (2) antibody-cytokine fusion protein technology; (3) chimeric immune receptor technology, and (4) antibody-HLA/peptide complex technology.