Transcytosis-Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging.

Transcytosis-based tubular reabsorption of endogenous proteins is a well-known energy-saving pathway that prevents nutrient loss. However, utilization of this well-known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2-targeted Gly-Sar peptide as a ligand, renal-clearable luminescent gold nanoparticles (P-AuNPs) were developed as protein mimics to investigate the transcytosis-based tubular reabsorption of exogenous substances. By regulating the influential factors (H+ content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly-Sar-mediated transcytosis, the specific and efficient interaction between P-AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P-AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high-contrast tumor imaging.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Cell response and bone ingrowth to 3D printed Ti6Al4V scaffolds with Mg-incorporating sol-gel Ta2O5 coating.

In recent years, additive manufacturing techniques have been used to fabricate 3D titanium (Ti)-based scaffolds for production of desirable complex shapes. However, insufficient osteointegration of porous Ti-based scaffolds can elicit long-term complications (e.g., aseptic loosening) and need further revision surgery. In this study, a magnesium (Mg)-incorporating tantalum (Ta) coating was deposited on a 3D Ti6Al4V scaffold using a sol-gel method for enhancing its osteogenic properties. To evaluate the biofunction of this surface, bone mesenchymal stem cells and rabbit femoral condyle were used to assess the cell response and bone ingrowth, respectively. Ta2O5 coatings and Mg-incorporating Ta2O5 coatings were both homogeneously deposited on porous scaffolds. In vitro studies revealed that both coatings exhibit enhanced cell proliferation, ALP activity, osteogenic gene expression and mineralization compared with the uncoated Ti6Al4V scaffold. Especially for Mg-incorporating Ta2O5 coatings, great improvements were observed. In vivo studies, including radiographic examination, fluorochrome labeling and histological evaluation also followed similar trends. Also, bone ingrowth to scaffolds with Mg-incorporating Ta2O5 coatings exhibited the most significant increase compared with uncoated and Ta2O5 coated scaffolds. All the above results indicate that Mg-doped Ta2O5 coatings are an effective tool for facilitating osteointegration of conventional porous Ti6Al4V scaffolds.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level.

Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Hypoglossal nerve delineation in nasopharyngeal carcinoma patients may reduce the radiation dose and damage to the nerve.

This study aims to establish a delineation guideline for the contouring of the hypoglossal nerve by dividing the nerve into different segments, and to test the possibility of a radiation dose reduction to the hypoglossal nerve in NPC patients receiving radiotherapy. Twenty NPC patients were selected arbitrarily. The hypoglossal nerves were delineated using anatomic landmarks and divided into the cisternal, intracanalicular, carotid, and transverse segments. The tumor coverage by radiation and dose-volume parameters of the nerve with and without various dose constraints to the hypoglossal nerve were compared. The hypoglossal nerve, which is invisible on CT images, can be delineated accurately with the assistance of several anatomic landmarks. Without a dose constraint to the hypoglossal nerve, the carotid space, intracanalicular, and transverse segments had high radiation dose-volumes. The dose-volume to the nerve, however, can be reduced when the nerve was defined and a dose constraint was given. The delineation of the hypoglossal nerve with its different segments is feasible. The carotid space, intracanalicular, and transverse segments received the highest dose, where the nerve damage was most likely located. The dose to the nerve can be reduced to less than 70 Gy using the intensity-modulated radiotherapy technique.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction.

BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.

Pancreatic Cancer and its Attributable Risk Factors in East Asia, Now and Future.

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.

Glutathione-Activated Emission of Ultrasmall Gold Nanoparticles in the Second Near-Infrared Window for Imaging of Early Kidney Injury.

Biomarker-activatable luminescent probes with high sensitivity and specificity show great promise in advanced bioimaging applications. However, the lack of stable biomarkers at an early stage is currently a major obstacle for sensitive early disease imaging. Herein, we develop a facile in vivo ligand exchange strategy to achieve renal-clearable activatable luminescent gold nanoparticles (AuNPs), which are independent of biomarkers for sensitive and long-time imaging of early kidney injury. Significantly activated emission in the second near-infrared region (∼1026 nm) is realized from the ligand exchange of triphenylphosphine-3,3',3″-trisulfonic acid (TPPTS)-coated AuNPs (∼1.4 nm, TPPTS-AuNPs) with quantitative amounts of glutathione (GSH). The abundant GSH in cells, particularly in liver sinusoids, is then demonstrated successfully to activate the emission of TPPTS-AuNPs with an extremely low background for both cell imaging and in vivo visualization of visceral organs (e.g., liver and kidneys). In addition, the in vivo GSH-exchanged TPPTS-AuNPs show enhanced interactions with acidic renal tubular epithelial cells, resulting in sensitive (contrast index, ∼3.9) and long-time (>6.5 h) noninvasive monitoring of acidosis-induced early kidney injury. This facile ligand exchange strategy opens new possibilities for designing activatable luminescent probes independent of biomarkers for earlier disease diagnosis and treatment.

Weak Anchoring Sites of Thiolate-Protected Luminescent Gold Nanoparticles.

Surface functionalization of gold nanoparticles (AuNPs) with thiolate ligands is a successful strategy for controlling their stability, nanotoxicity, circulation, and interaction with biological environments as leading nanomedicines. However, the effects of the weak anchoring groups of NH2 and COOH have been long-term ignored because of the well-recognized strong anchoring site of S-Au. Herein, the authors achieve controllable weak anchoring sites of the luminescent AuNPs using a typical thiolate peptide such as glutathione with anchoring groups of SH, COOH, and NH2 . Additionally, they establish that not only the strong anchoring site of S-Au, but also the weak anchoring sites from N-Au and COO-Au are critical to the behavior of AuNPs at both in vitro and in vivo levels. These results open up new possibilities for the fundamental understanding of the significance of the weak anchoring sites in the future surface functionalization of nanomedicines toward advanced theranostics.

Concentration-Dependent Subcellular Distribution of Ultrasmall Near-Infrared-Emitting Gold Nanoparticles.

The ability to accurately control the subcellular distribution of nanomedicines provides unique advantages on understanding of cellular biology and disease theranostics. The nanomedicine concentration is a key factor to affect the theranostic efficiency and systematic toxicity. Herein, we unravel a concentration-dependent subcellular distribution of near-infrared-emitting gold nanoparticles (AuNPs) co-coated with glutathione and a cell-penetrating peptide CR8 (CR-AuNPs), which shows a strong membrane-binding at high concentration but more endocytosis for mitochondria targeting at the low concentration region. Attributing to high content of AuI and microsecond luminescent lifetimes, these AuNPs can catalyze dissolved oxygen to generate singlet oxygen (1 O2 ) efficiently. Combining with the concentration-dependent subcellular distribution, the luminescent AuNPs show photocytotoxicity in the relative low concentration region. These findings facilitate the fundamental understanding of the biological behaviors and potential cytotoxicity of ultrasmall luminescent AuNPs toward future theranostics.

Precisely Regulated Luminescent Gold Nanoparticles for Identification of Cancer Metastases.

The nanoprobes for identification of cancer metastases in the mononuclear phagocyte system (MPS) organs are of significant importance but are limited due to the long-standing challenge of low tumor-targeting specificity with inadequate targeting efficiency and high nonspecific accumulation. Here, we report a surface regulation strategy that integrates the tumor-acidity-activated charge-reversal behavior and precise control in both hydrodynamic diameter (HD) and surface charge on ultrasmall luminescent gold nanoparticles (AuNPs) to achieve significantly high tumor-targeting specificity. The precise regulation of AuNPs to a rational HD and surface charge could rapidly and selectively recognize small metastatic tumors (∼1 mm) in liver and lung with high signal-to-noise ratios of 4.6 and 4.5, respectively. These results help further understand the in vivo transport of nanoprobes and provide guidance for design of translatable nanosized nanomedicines in cancer metastasis theranostics.

PIM-1 may function as an oncogene in cervical cancer via activating the EGFR signaling.

BACKGROUND: This work was designed to explore the roles of PIM-1 in the development of cervical cancer. METHODS: There were 90 paired cervical tumor samples and the non-tumor adjacent tissue. The levels of PIM-1 in different samples were examined using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) methods. The potential diagnostic value of PIM-1 was analyzed by the receiver operating characteristic (ROC) curve; furthermore, the expression of EGFR in tumor samples was detected, and Pearson's correlation analysis was performed to analyze the relationship between the expression of PIM-1 and EGFR. Finally, cervical cancer cell line Hela cells were cultured and treated by PIM-1 siRNA, and MTT assay and Pi/Annexin V assay were performed to explore the effects of PIM-1 siRNA on the growth and apoptosis ability of the Hela cells. RESULTS: PIM-1 was significantly up-regulated in cervical cancer tissue compared to adjacent tissue, and the expression of PIM-1 in patients with cervical cancer is positively associated with the size and metastasis of the tumor. ROC analysis showed PIM-1 is a sensitive biomarker for the diagnosis of cervical cancer. Furthermore, EGFR was over-expressed in cervical cancer tumor tissues, and the levels of PIM-1 and EGFR in cervical cancer tissue were positively correlated. Finally, PIM-1 siRNA dramatically inhibited the viability and promoted the apoptosis of the Hela cells. CONCLUSION: Our findings prove that PIM-1 may function as an oncogene in cervical cancer and can regulate the EGFR signaling in cervical cancer.

Strict DNA Valence Control in Ultrasmall Thiolate-Protected Near-Infrared-Emitting Gold Nanoparticles.

Realizing robust DNA functionalization with strict valence control in the sub-2-nm thiolate-protected luminescent gold nanoparticles (AuNPs) is highly demanded but remains unsolved due to their unique Au(0) core and Au(I)-S shell structures. Herein, we report a facile strategy using phosphorothioates (ps)-modified DNA (psDNA) as a template for in situ growth of near-infrared (NIR)-emitting AuNPs with precisely controlled DNA valence. In addition, the particle size could be finely tuned in ultrasmall ranges from 1.3 to 2.6 nm with regulation of the ps length of psDNA. The ultrasmall NIR-emitting AuNPs bearing strict DNA valence are also demonstrated to be as powerful building block for well-organized one-dimensional assembly and optical probe for targeted cellular imaging. Such a facile strategy in decoration of luminescent AuNPs with strict DNA valence provides a new pathway for development of surface-functionalizable ultrasmall metal nanoplatforms toward various downstream applications.

Heart-sparing effect of postmastectomy radiotherapy for breast cancer patients: A dosimetric study of cardiac substructures.

We investigated to what extent can the dose-volumes of the coronary artery and the cardiac substructures be reduced by using IMRT technique in left-sided breast cancer patients. We chose 40 pN2M0 patients treated with postmastectomy IMRT. The original treatment plans were retrieved and the (internal mammary nodes) IMNs and cardiac substructure delineations were added. Three sets of dose-volume parameters including the original plans without internal mammary irradiation (IMNI), the plans with IMNI, and the plans with dose constraints to the heart, were derived. In left-sided patients, when IMNI was included, the V30 for right ventricle (RV), left ventricle (LV), pulmonic valve (PV), and left anterior descending artery (LADA) were 56.37% ± 7.9%, 25.3% ± 7.3%, 48.3% ± 6.3%, and 69.7% ± 6.4%, respectively. Of the 4 main coronary arteries, LADA had the highest dose followed by the left main coronary artery (LMCA). LADA had a V40 of 62% ± 9.7% vs 13.5% ± 3.5%, and a V50 of 27.5% ± 4.7% vs 0, with and without IMNI. For the right-sided patients, the V30s for all the heart substructures were 0 with or without IMNI. When we set a dose constraint of V40 < 10% for the LADA in the left-sided patients, the PTV volumes covered by 50 Gy decreased by only 1%. IMNI increased the V30 of the right and left ventricle and significantly increased the V40 and V50 to the LADA of left-sided breast cancer patients. IMRT markedly reduces the dose to the main coronary arteries and the right and left ventricle.

Risk analysis on infection caused by peripherally inserted central catheter for bone tumor patients.

OBJECTIVE: The aim of this study is to explore the related factors affecting infection risk caused by peripherally inserted central catheter (PICC) for bone tumor patients. METHOD: A retrospective analysis was performed for 223 bone tumor patients who received PICC and were admitted to our hospital from 2004 to 2017. A total of 18 cases (infection group) with PICC catheter-related infections and 205 cases without infection (noninfection group) were studied. First, factor analysis of variance or Chi-square test was applied to compare independent risk factors for PICC catheter-related infections, between bone tumor patients with catheter-related infections and those without catheter-related infections. RESULTS: This retrospective analysis involved a total of 18 patients with PICC infections and 205 patients without infections. The infection rate was 8.07%. Factor analysis of variance showed that many factors were related to PICC catheter-related infections, including experience of operator (χ2 = 3.48, P < 0.05), catheter retention time (χ2 = 7.478, P < 0.05), receiving chemotherapy or not (χ2 = 2.43, P < 0.05), Karnofsky Performance Scale scores (χ2 = 2.19, P < 0.05) and the frequency of replacing pad pasting on the point of puncture (χ2 = 2.23). Logistic regression analysis showed that PICC catheter retention time (odds ratio [OR] = 4.21, P < 0.05) and operator experience (OR = 2.80, P < 0.05) were independent factors affected PICC catheter-related infections. CONCLUSION: Catheter-related infections were related to experience of PICC operatorand length of catheter retention time.

CASP8 -652 6N insertion/deletion polymorphism and overall cancer risk: evidence from 49 studies.

The CASP8 -652 6N insertion/deletion (I/D) polymorphism reduces expression of caspase 8. We conducted a meta-analysis to clarify the relationship between this polymorphism and cancer risk. Eligible articles were retrieved from PubMed, EMBASE, CNKI, and WANFANG databases through February 2017. A total of 33 articles with 49 studies, including 33,494 cases and 36,397 controls, were analyzed. We found that the CASP8 -652 6N ins/del polymorphism was associated with decreased overall cancer risk in five genetic models [DD vs. II: odds ratio (OR)=0.76, 95% confidence interval (CI)=0.69-0.84, ID vs. II: OR=0.87, 95% CI=0.83-0.92, DD vs. ID/II: OR=0.82, 95% CI=0.75-0.89, ID/DD vs. II: OR=0.85, 95% CI=0.80-0.90, and D vs. I: OR=0.87, 95% CI=0.83-0.91]. Stratified analyses showed that the polymorphism was associated with decreased risk of colorectal, breast, esophageal, renal cell, lung, cervical, bladder, gastric, and other cancers. Overall cancer risk was reduced in Asian and Caucasian patients, both hospital- and population-based studies, and both high and low quality studies. Our results highlight the role of the CASP8 -652 6N ins/del polymorphism in decreasing cancer risk. Further studies with large-cohort populations, especially for specific cancer types and ethnic groups, are needed to confirm our findings.

[Usefulness of self-made gasbag double-cannula stool drainage device for prevention of anastomotic leakage following anterior resection].

OBJECTIVE: To evaluate the efficacy of self-made gasbag double-cannula stool drainage device for prevention of anastomotic leakage following anterior resection. METHODS: Clinical data of 169 rectal cancer patients in the 8th Affiliated Hospital of Sun Yat-sen University between October 2010 and October 2016 were retrospectively analyzed. Among them, a self-made gasbag double-cannula stool drainage device was placed in 71 patients(stool drainage group), and the remaining 98 patients were taken as control. After an anastomosis, the drainage device was transanally placed by the assistant and the distal tube of drainage device was stretched more than 15 cm from anastomosis. The gasbag was inflated to fully expand the intestine. The main tube was fixed on perianal skin with 7-0 suture, kept more than 3-5 cm outside the anus, and connected to the drainage bag. The incidence of anastomotic leakage was compared between the two groups. RESULTS: The baseline data were similar between the two groups (all P>0.05). The differences in operative time, intraoperative blood loss, and time to bowel function recovery were not statistically significant (all P>0.05), however, time to oral intake and postoperative stay were shorter in stool drainage group as compared to the control group (both P<0.05). There was no perioperative death in both groups. In stool drainage group, there were 6 cases whose drainage device was pulled out within 48 hours due to intolerance. The ruptured gasbag was replaced 5 times and the tube was clogged by fecal material 21 times. After flushing, the tube did not recanalized and was pulled out in 3 cases. The incidence of anastomotic leakage in stool drainage group was significantly lower than that in the control group (2.8% vs. 11.2%, P=0.043). As for the low anastomosis (the distance to anal verge less than 5 cm), the incidence of anastomotic leakage in stool drainage group was also significantly lower than that in the control group (2.3% vs. 15.4%, P=0.028), while as for the high anastomosis, the difference was not statistically significant (3.6% vs. 3.0%, P=0.906). Logistic regression analysis revealed that the presence of a stool drainage device was an independent protective factor for anastomotic leakage (OR=0.316, 95%CI:0.114 ~ 0.769, P=0.003). CONCLUSIONS: The self-made gasbag double-cannula stool drainage device effectively prevents anastomotic leakage after anterior resection of rectal cancer. However it is not suitable for those patients with high anastomosis.

[Reasons for anastomotic leakage following the learning curve by laparoscopic anterior resection of rectal cancer].

OBJECTIVE: To investigate the reasons of anastomotic leakage following learning curve by laparoscopic anterior resection of rectal cancer.
 Methods: From December, 2011 to March, 2015, the clinical information of 179 patients in our hospital who underwent dixon of rectal cancer were collected. The patients were divided into a laparoscopic learning group, a laparotomy group and a laparoscopic group. The reasons of anastomotic leakage for each group were comparatively analyzed. Repeated cutting of anastomotic stoma was compared between the laparoscopic learning group and the laparoscopic group. The male, age, obesity, nutrition complications and the position of anastomotic stoma were compared among the 3 groups.
 Results: The rate of anastomotic leakage in the laparoscopic learning group was significantly higher than that in the laparotomy group and the laparoscopic group (P<0.05). Repeated cutting was a significant risk factor in the laparoscopic learning group (P<0.05), but not in the laparoscopic group. Except obesity, the four factors were significant risk factors in the laparoscopic learning group (P<0.05). All of the five factors were not the significant risk factors in the laparotomy group and the laparoscopic group (P>0.05).
 Conclusion: The operation technical shortcoming is the major factor in the learning of the laparoscopic anterior resection of rectal cancer. In order to reduce the rate of anastomotic leakage in the learning curve period, the selection of patients following the laparoscopic anterior resection of rectal cancer should avoid the following factors: male, older age, the low position of the tumor and the nutrition complications.

The efficacy assessments of alkylating drugs induced by nano-Fe3O4/CA for curing breast and hepatic cancer.

A new method to evaluate the anticancer activity at the molecular level has been developed. In our assay, the interaction between alkylating anticancer drugs-Fe3O4/CA with DNA has been investigated for the Resonance Light Scattering (RLS) signal enhancement. Water-based nano-Fe3O4, as a probe, has the ability of good solubility, biodegradability and low bulk resistivity etc. The experimental results show that, the activity order of three kinds of drugs is Nimustine (ACNU)>Semustine (Me-CCNU)>Chlormethine (HN2), which is satisfied with the results of the cell apoptosis experiment and the IC50 by MTT method. This assay is simple, sensitive and high efficient. And the theoretical basics for the development of new anticancer drugs as well as the assessments of their efficacy to cure breast and hepatic cancer have been provided.

Establishment and characterization of GCSR1, a multi-drug resistant signet ring cell gastric cancer cell line.

Signet ring cell gastric cancer (SRCGC) has very poor prognosis worldwide, and studying its molecular characteristics is urgent for improving the outcome. However, few well-characterized SRCGC cell lines are available for research. Therefore, we established a novel cell line GCSR1, from a Chinese male SRCGC patient. Cell morphology of GCSR1 in culture, maintained in vitro for over 90 passages, is similar to the cells from the patient. GCSR1 cells proliferated in vitro with a doubling time of 67.65 h. Karyotyping showed they were aneuploid. Missense mutation occurred in codon 193 of P53 and deletion occurred in exons 1 and 3 of P16. Results of CCK8 assay revealed that GCSR1 was more resistant to 5-fluorouracil (5-FU) and mitomycin (MMC) than other gastric cancer cell lines. Stem cell marker assay by flow cytometry showed that GCSR1 had high proportion of CD44+ and/or CD133+ cells. It formed colonies easily in soft agar and generated xenograft tumors in nude mice. In conclusion, GCSR1 is a well-established, well-characterized multi-drug resistant cell line with abundant cancer stem cells.