Knockdown of miR-24 Suppressed the Tumor Growth of Cervical Carcinoma Through Regulating PTEN/PI3K/AKT Signaling Pathway.

Cervical cancer (CC) is the most prevalent malignant tumor in gynecology. Despite routine surgery, advanced CC is hard to remove completely. MicroRNA-24 (miR-24) regulates several types of tumors, but its regulatory function in CC was previously unknown. We established stable knockdown of miR-24 and phosphatase and tensin homolog (PTEN) in CC cells. We measured mRNA and protein expression with RT-PCR and western blotting. We evaluated cell proliferation, invasion, migration, and apoptosis with CCK8, Transwell, wound healing, and flow cytometry, respectively. We also examined the influence of miR-24 and PTEN on tumor growth in a metastatic tumor model in nude mice. The expression of miR-24 was significantly increased in CC tissues and cell lines (C-33A, HeLa S3, SiHa). MiR-24 inhibitor greatly suppressed PTEN/PI3K/AKT, while miR-24 mimic markedly activated this signaling pathway. Knockdown of PTEN significantly reversed the effects of miR-24 inhibitor on cell proliferation, invasion, migration, and apoptosis of CC cells. The significant inhibition effect of tumor growth and ki67 expression caused by miR-24 inhibitor was reversed by si-PTEN. MiR-24 inhibitor significantly suppressed cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) process, and tumor growth, while promoting cell apoptosis. However, the influence of miR-24 inhibitor was markedly reversed by si-PTEN. Targeting miR-24 could provide a novel therapeutic strategy for the prevention and treatment of CC.

Down-regulation of miR-424 inhibited the metastasis of endometrial carcinoma via targeting PTEN/PI3K/AKT signaling pathway.

Background: The incidence of endometrial carcinoma (EC) has been increasing annually, and treatment of advanced cases remains challenging. MicroRNA-424 (miR-424) was reported to affect several types of tumors, but its role in EC has not been studied. Methods: We generated transient knockdown models of miR-424 and PTEN in EC cells. We measured mRNA and protein expression using RT-PCR and western blotting. We evaluated cell proliferation, invasion, migration, and apoptosis using CCK8, Transwell, wound healing, and flow cytometry assays. We also investigated the effect of miR-424 and PTEN on tumor growth using a metastatic tumor model in nude mice. Results: The expression of miR-424 was significantly elevated in EC tissues and cell lines. MiR-424 inhibitor significantly restrained PTEN/PI3K/AKT signaling, while miR-424 mimic activated this pathway. Knockdown of PTEN significantly reversed the effects of miR-424 inhibitor on cell proliferation, invasion, migration, and apoptosis in EC cells. The significant inhibition of tumor growth and ki67 expression caused by miR-424 inhibitor were markedly promoted by sh-PTEN. Conclusions: Our findings suggest that miR-424 inhibitor could inhibit cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) process, and tumor growth, while promoting apoptosis in EC. However, the effects of miR-424 inhibitor were markedly reversed by sh-PTEN. This study provides a potential novel therapeutic strategy for the prevention and treatment of EC by targeting miR-424.

Prognostic value of apparent diffusion coefficient in neuroendocrine carcinomas of the uterine cervix.

Objectives: This research was designed to examine the associations between the apparent diffusion coefficient (ADC) values and clinicopathological parameters, and to explore the prognostic value of ADC values in predicting the International Federation of Gynecology and Obstetrics (FIGO) stage and outcome of patients suffering from neuroendocrine carcinomas of the uterine cervix (NECCs). Methods: This retrospective study included 83 patients with NECCs, who had undergone pre-treatment magnetic resonance imaging (MRI) between November 2002 and June 2019. The median follow-up period was 50.7 months. Regions of interest (ROIs) were drawn manually by two radiologists. ADC values in the lesions were calculated using the Functool software. These values were compared between different clinicopathological parameters groups. The Kaplan-Meier approach was adopted to forecast survival rates. Prognostic factors were decided by the Cox regression method. Results: In the cohort of 83 patients, nine, 42, 23, and nine patients were in stage I, II, III, and IV, respectively. ADCmean, ADCmax, and ADCmin were greatly lower in stage IIB-IVB than in stage I-IIA tumours, as well as in tumours measuring ≥ 4 cm than in those < 4 cm. ADCmean, FIGO stage, and age at dianosis were independent prognostic variables for the 5-year overall survival (OS). ADCmin, FIGO stage, age at diagnosis and para-aortic lymph node metastasis were independent prognostic variables for the 5-year progression-free survival (PFS) in multivariate analysis. For surgically treated patients (n = 45), ADCmax was an independent prognostic parameter for both 5-year OS and 5-year PFS. Conclusions: ADCmean, ADCmin, and ADCmax are independent prognostic factors for NECCs. ADC analysis could be useful in predicting the survival outcomes in patients with NECCs.

A novel conversion strategy for organic compounds in waste liquid crystal displays based on the near/supercritical methanol process.

Waste liquid crystal displays (LCD) contain a large number of organic compounds such as cellulose triacetate (CTA), poly(vinyl alcohol) (PVA), triphenyl phosphate (TPP), and liquid crystal (LC). It is important to recover organic compounds from waste LCD due to their value and environmental toxicity. However, it is challenging to recover organic compounds from waste LCD because of the heterogeneous mixture of glass, organics and metals contained therein. In this study, an environment-friendly near/supercritical methanol (NSCM) process was developed as a closed cycle technology for the conversion of organic compounds from waste LCD. The acid-base catalytic activity and nonpolar property of the NSCM could efficiently promote the conversion of organic compounds from waste LCD. TPP could be extracted below 200 °C in the NSCM process. Below 250 °C, the conversion ratio of organic compounds from waste LCD ranged from 5 % to 68 % due to the extraction or decomposition of TPP, LC, and PVA. The main products obtained at 250 °C included long-chain alcohols and alkanes with a similar composition to industrial liquid paraffin, which could be widely used in other industrial processes. Under the optimal operation parameters (300 °C, 30 min, and 1:20 g/ml), the conversion ratio of organic compounds could reach 98 % due to the efficient decomposition of CTA. The main products obtained included ketones and esters chemicals, which could be further used as a chemical feedstock. No secondary pollutant was generated in the whole process. The low-boiling methanol could easily be recycled, which could make the NSCM a clean process for the production of high value-added organic products from waste LCD.

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study.

Objective: This study analyzed metabolic factors associated with lymphovascular space invasion (LVSI) and compared the difference between type 1 and type 2 endometrial cancer (EC). Methods: Four hundred patients primarily diagnosed with EC who underwent hysterectomy with pathological results at Fujian Medical University Cancer Hospital from January 2019 to January 2021 were included. Demographic variable data were collected as well as pathological results. Laboratory evaluations included fasting blood glucose (FBG), serum cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (Apo A) and apolipoprotein B (Apo B). Characterization of binary logistic regression models was used to test the odds ratios (ORs) between LVSI and its metabolic parameters with different subtypes of EC. Results: The results indicated that CA125, ROMA, Ki67 score, FBG and TC were higher in EC patients with LVSI (all p<0.05). Negative ER and PR expression was positively associated with LVSI (P<0.05). CA125, ROMA, FBG, TC and ER were found to be independent risk factors for LVSI. CA125, ROMA and FBG were significantly elevated in type 1 EC patients with LVSI compared with those without LVSI (all p<0.05). TC and Ki67 scores were much higher in type 2 EC patients with vs without LVSI (all p<0.05). Negative PR expression was positively related to both type 1 and type 2 EC patients with LVSI. Consequently, CA125, ROMA, FBG and Apo B were found to be independent risk factors for LVSI in type 1 EC, and TC was found to be an independent risk factor for LVSI in type 2 EC. Conclusion: FBG and TC were both independent risk factors for LVSI in EC. FBG and Apo B were independent risk factors for LVSI in type 1 EC. TC was an independent risk factor for LVSI in type 2 EC.

Ultrasensitive and practical chemiluminescence sensing pesticide residue acetamiprid in agricultural products and environment: Combination of synergistically coupled co-amplifying signal and smart interface engineering.

Practical detection of single-component pesticide residue at ultra-low concentrations in agricultural products and environment is very important for assessment of environmental risks and protection of human health. Herein, a practical and highly sensitive chemiluminescence (CL) sensing acetamiprid in agricultural products and environmental media was constructed based on the synergistic co-catalysis of graphene oxide (GO)/gold nanoparticles (AuNPs) nanocomposites for luminol CL reaction and the smart interface engineering. ss-DNA could inhibit co-catalysis of GO/AuNPs for luminol CL reaction. Once acetamiprid was added, aptamer conformation changed in dimension and synergistically catalytic amplification signal of GO/AuNPs was restored significantly. The limit of detection was 8.9 pM. High sensitivity could be due to strong signal amplification from synergistic catalysis of GO/AuNPs for CL reaction and perfect regulation of composite interface by DNA dimension. Moreover, the used GO/AuNPs could be stably stored for six months, which was superior to previously reported AuNPs (only half a month). The analysis exhibited excellent selectivity for acetamiprid. The detection results for real samples confirmed reliability in practical application. This analysis is an extremely useful method for monitoring pesticide residues in environment and agricultural products. Synergetic co-catalysis of GO/AuNPs and ingenious interface engineering provide important ideas for other biosensors.

Prognostic factors and treatment of neuroendocrine tumors of the uterine cervix based on the FIGO 2018 staging system: a single-institution study of 172 patients.

OBJECTIVE: This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. METHODS: A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. RESULTS: Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I-IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I-IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I-IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I-IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). CONCLUSION: Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs.

Ultraeven Mo-Doped CoP Nanocrystals as Bifunctional Electrocatalyst for Efficient Overall Water Splitting.

To develop precious-metal-free bifunctional catalysts for overall water splitting, ultraeven Mo-doped CoP composites (Mo-CoP) have been fabricated by an in situ phosphorization protocol using CoMo-layered double hydroxide (CoMo-LDH) as the precursor. The ordered arrangement of cations in the CoMo-LDH could be easily phosphored and generate the ultraevenly dispersed Mo element within the CoP structure, resulting in the excellent bifunctional catalyst for overall water splitting. The hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) catalytic activities of the composites present an increase first and then a decreasing tendency with increased Mo doping content. Among all the Mo-doped CoP materials, the composite with a Mo/Co mole ratio of 1/2.3 presents the highest HER activity and stability in acidic conditions. At the current density of -10 mA·cm-2 in 0.5 M H2SO4, the overpotential is only 116 mV. In addition, the composite also presents excellent HER and OER performance under alkaline conditions. The overpotential is 118 mV for HER and 317 mV for OER at 10 mA cm-2 in 1 M KOH. It requires a cell voltage of 1.7 V to achieve a current density of 10 mA·cm-2 and maintains a stable water-splitting current for at least 24 h, which is superior to most reported alkaline media. This simple and efficient synthetic approach could also be used for ultraeven doping between other transition metal ions.

Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0-1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database.

BACKGROUND: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0-1/M0 ILC. METHODS: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Aiming to minimize the selection bias of baseline characteristics, Propensity Score Matching (PSM) method was used. RESULTS: In a total of 12,334 patients with HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC, 1785 patients (14.5%) were allocated into adjuvant chemotherapy group and 10,549 (85.5%) into control group. Used PSM, the 1785 patients in adjuvant chemotherapy group matched to the 1785 patients in control group. By Kaplan-Meier survival analyses, we observed no beneficial effect of adjuvant chemotherapy on OS in both original samples (P = 0.639) and matched samples (P = 0.962), however, ineffective or even contrary results of adjuvant chemotherapy on BCSM both in original samples (P = 0.001) and in matched samples (P = 0.002). In both original and matched multivariate Cox models, we observed ineffectiveness of adjuvant chemotherapy on OS (hazard ratio (HR) for overall survival = 0.82, 95% confidence interval (CI) [0.62-1.09]; P = 0.172 and HR = 0.90, 95%CI [0.65-1.26]; P = 0.553, respectively), unexpectedly promoting effect of adjuvant chemotherapy on BCSM (HR = 2.33, 95%CI [1.47-3.67]; P = 0.001 and HR = 2.41, 95%CI [1.32-4.39]; P = 0.004, respectively). Standard surgery was beneficial to the survival of patients. Lymph node metastasis was detrimental to survival and radiotherapy brought survival benefit in original samples, but two issues had unobvious effect in matched samples. CONCLUSION: In this study, adjuvant chemotherapy did not improve survival for patients with HR-positive, HER2-negative pT1b-c/N0-1/M0 ILC.

DEHP degradation and dechlorination of polyvinyl chloride waste in subcritical water with alkali and ethanol: A comparative study.

In this study, subcritical water-NaOH (CW-NaOH) and subcritical water-C2H5OH (CW-C2H5OH) processes were developed for diethylhexyl phthalate (DEHP) degradation and dechlorination of polyvinyl chloride (PVC) waste. The introduction of NaOH or C2H5OH in subcritical water had a noticeable influence on the mechanism of DEHP degradation and dechlorination. For both CW-NaOH and CW-C2H5OH treatments, the increase in temperature could increase dechlorination efficiency (DE) of PVC. The DE of CW-NaOH is much higher than that of CW-C2H5OH under the same conditions. The DE of CW-NaOH could exceed 95% at 300 °C. Hydroxyl nucleophilic substitution was the main dechlorination mechanism in CW-NaOH, while nucleophilic substitution and direct dehydrochlorination were equally important in CW-C2H5OH. In CW-NaOH treatment, 2-ethyl-1-hexanol, benzaldehyde, and toluene were obtained by hydrolysis and reduction reactions of DEHP. Acetophenone was produced by the further cyclization, dehydrogenation and rearrangement reactions of 2-ethyl-1-hexanol. Transesterification was the main degradation pathway of DEHP in CW-C2H5OH at 300 °C. The cyclization and dehydration of 2-ethyl-1-hexanol resulted in producing a high level of ethyl-cyclohexane and 1-ethyl-cyclohexene in CW-C2H5OH at 350 °C. Furthermore, high concentration of ethyl palmitate and ethyl stearate could be prepared in CW-C2H5OH system by the strong reactivity of C2H5OH with the lubricants in PVC.

Practical aptamer-based assay of heavy metal mercury ion in contaminated environmental samples: convenience and sensitivity.

Due to heavy metals' magnified pollution from their accumulation in the ecosystem, practical detection of ultra-low concentration of heavy metals in environmental sample is of great significance for environmental supervision and maintenance of people's health. Herein, a practical and sensitive assay of heavy metal mercury was developed by visually observing (or spectrum detecting) the change of cationic gold nanoparticles (AuNPs), which is directly caused by mercury ion induced hybridization between non-canonical base pairs. In this assay, signal probe's response was direct rather than the indirect salt induction, thus avoiding the defect of salt-induced indirect response. It makes the analysis more sensitive. The results showed that the response of 8.2 × 10-8 M Hg2+ could be observed with naked eye and the detection limit of Hg2+ in spectrometric determination was 4.9 × 10-11 M, which is more than one order of magnitude lower than that from indirect response pattern of signal probe. In addition, high specificity of the affinity chemistry for T-Hg-T renders the assay to be highly selective. Compared with the results of cold vapor atom adsorption spectroscopy (CVAAS), this analysis has good reliability for the detection of mercury. The results fully indicate that the developed assay is an ideal alternative for online detection of heavy metal mercury in environmental pollution samples.

A novel safety treatment strategy of DEHP-rich flexible polyvinyl chloride waste through low-temperature critical aqueous ammonia treatment.

Flexible polyvinyl chloride (f-PVC) contains high content of plasticizers and chlorine. Improper treatment of waste f-PVC can easily lead to resource wasting and bring environmental risks. In this work, a novel strategy for resource recycling and dechlorination of waste f-PVC containing high content of di-(2-ethylhexyl) phthalate (DEHP) was developed by using low-temperature critical aqueous ammonia (LCA) process. The LCA treatment of waste DEHP-rich f-PVC (WDP) was performed at the temperature range of 200-400 °C with the ammonia concentration of 1%-5%. The results indicated that the LCA temperature had a significant effect on the chemical composition of decomposition products. High concentration of 2-ethyl-1-hexanol (86.12%), which is an important chemical feedstock and is derived from the decomposition of DEHP, could be obtained from WDP by the LCA process at 250 °C, and the concentration of 2-ethyl-1-hexanol decreased markedly with increasing the temperature. Benzaldehyde and acetophenone were generated when the temperature increased to 300 °C, and their concentrations increased with the rise of temperature. The increase of the ammonia concentration and the temperature could enhance the dechlorination efficiency of WDP. The dechlorination could reach 98.7% at 300 °C. This result showed that the LCA process was a promising and high-efficiency strategy for the sustainable management of WDP.

A novel management strategy for removal and degradation of polybrominated diphenyl ethers (PBDEs) in waste printed circuit boards.

Waste printed circuit boards (PCBs) contain a high level of brominated flame retardants (BFRs), among which polybrominated biphenyl ethers (PBDEs) are the most widely used additive BFRs. PBDEs are considered to be a type of persistent organic pollutants (POPs). The efficient removal/degradation of PBDEs in waste PCBs is an urgent problem in electronic waste treatment, but the degradation of PBDEs is a great challenge due to their extreme stability and persistence in nature. In this study, a novel management strategy was developed for removal and degradation of PBDEs in waste PCBs by using a simple subcritical methanol (SubCM) process. The results showed that reaction temperature, residence time, solid-to-liquid ratio, and additive NaOH are key factors influencing the removal of PBDEs from waste PCBs. Under optimal conditions (200 °C, 60 min, 1:20 g/mL), the removal efficiency of ∑8PBDEs from waste PCBs could reach 91.3% and 98.8% for the proposed process of SubCM and SubCM + NaOH, respectively. When the temperature is below 200 °C, highly brominated PBDEs congeners in waste PCBs were degraded into 2,'3,4',6-Tetrabromodiphenyl ether (BDE71) and 2,4,4'-Tribromodiphenyl ether (BDE28) after SubCM treatment. 4-Bromophenyl ether (BDE4) and diphenyl ether were generated by the further debromination of BDE71 and BDE28 with the increase of treatment temperature. The debromination temperature of PBDEs congeners in SubCM could be markedly lowered by adding 4 g/L of NaOH. The complete debromination of PBDEs congeners in waste PCBs could be achieved at 300 °C and 250 °C for the developed process of SubCM and SubCM + NaOH, respectively.

A facile chemiluminescence sensing for ultrasensitive detection of heparin using charge effect of positively-charged AuNPs.

Heparin is a glycosaminoglycan with the highest negative charge density of any known biological molecule. Herein, this highly negative charge structure of heparin and the charge effect from positively-charged AuNPs for luminol chemiluminescence (CL) reaction were combined to build a facile and sensitive CL strategy for detection of heparin. The highly negative charge structure of heparin molecules (four negatively-charged side groups per repeat unit) and the effective signal amplification of charge effect from positively-charged AuNPs make this analysis to display high sensitivity for heparin detection, and the detection limit is as low as 0.06 ng/mL. It is about two orders of magnitude lower than the previously reported colorimetric assay and far lower than the current analysis methods. The established CL strategy is to use the electrostatic interaction between heparin and signal probe (positively-charged AuNPs). Since polyanionic heparin has the highest negative charge in biological system, this CL sensing shows high selectivity for the detection of heparin, and hyaluronic acid (HA), an analogue of heparin, cannot cause interference. This CL sensing succeeded in detecting heparin in human serum samples. Besides, polycationic protamine, heparin antidote, can respond to the system's CL signals through its strong interactions with heparin, thus indirectly detecting protamine. For protamine in serum samples, the detection result was basically consistent with Coomassie brilliant blue assay.

A novel treatment of waste printed circuit boards by low-temperature near-critical aqueous ammonia: Debromination and preparation of nitrogen-containing fine chemicals.

In waste printed circuit boards (PCBs), brominated epoxy resin (BER) and copper are the two types of material that attracts the most attention due to their environmental risk and resource value. In this study, a novel and high-efficiency process for debromination and resource recovery of waste PCBs by low-temperature near-critical aqueous ammonia (NCAA) was successfully developed. A batch reactor was used in experiments with the temperatures ranging from 200 to 350 °C and the reaction times from 30 to 90 min. The ammonia water in near critical conditions can act not only as a medium but also as a reactant. Approximately 100% of the Br in waste PCBs could be removed and trapped by the NCAA at 300 °C. Copper foil could be easily separated and recovered from waste PCBs after the NCAA process. No brominated organic compounds could be detected in the oil phase products after the NCAA treatment of waste PCBs even at low temperature of 200 °C. Two new products (pyrazine and pyridine compounds) with high value-added were obtained for the first time by the treatment of waste PCBs. This study provides a novel and efficient strategy for the debromination, the recovery of copper, and the preparation of high value-added nitrogen-containing fine chemicals from waste PCBs. The low-temperature NCAA processing of waste PCBs could effectively reduce the energy consumption in comparison with traditional thermal decomposition processes, and promote the sustainable waste management strategy for waste electrical and electronic equipment (WEEE).

Human breast carcinoma xenografts in nude mice.

OBJECTIVE: To investigate spontaneous metastasis, micrometastasis and genetic stability in human breast carcinoma xenografts in nude mice. METHODS: Intact tissue from surgical specimens from breast carcinoma patients was xenografted into nude mice and transplanted from generation to generation. Cells from the xenografts were cultured in vitro and retransplanted into nude mice. Microsatellite DNA in the genome of human breast carcinomas, xenotransplanted tumors and metastases in nude mice were analyzed at three microsatellite loci. RESULTS: The tumorigenicity of orthotopic xenotransplantation was 88.6% (31/35), with a metastatic rate of 41.9% (13/31). Cells from xenotransplants were successfully cultured in vitro. The taking rate of retransplantation into nude mice and the spontaneous lung metastasis rate were both 100% (10/10). Microsatellite DNA sequences in the genome of xenotransplanted tumors and metastases in nude mice were identical with that of the original human breast carcinoma at three microsatellite loci. CONCLUSIONS: Tumorigenicity and metastatic potential can be improved in human breast carcinoma xenografts using intact fresh tumor tissue and orthotopic grafts. Xenotransplanted tumors and tumors after serial passage maintained the genetic stability. The detection of microsatellite DNA may identify micrometastases in a nude mouse model.