A Double-Layer Polyurethane Electrospun Membrane with Directional Sweat Transport Ability for Use as a Soft Strain Sensor.

Wearable electronics for long-term monitoring of physiological signals should be capable of removing sweat generated during daily motion, which significantly impacts signal stability, human comfort, and safety of the electronics. In this study, we developed a double-layer polyurethane (PU) membrane with sweat-directional transport ability that can be applied for monitoring strain signals. The PU membrane was composed of a hydrophilic, conductive layer and a relatively hydrophobic layer. The double-layer PU composite membrane exhibited varied pore size and opposite hydrophilicity on its two sides, enabling the spontaneous pumping of sweat from the hydrophobic side to the hydrophilic side, i.e., the directional transport of sweat. The membrane can be used as a strain sensor to monitor motion strain over a broad working range of 0% to 250% with high sensitivity (GF = 4.11). The sensor can also detect simple human movements even under sweating conditions. We believe that the strategy demonstrated here will provide new insights into the design of next-generation strain sensors.

The value of quantitative shear wave elastography combined with conventional ultrasound in evaluating and guiding fine needle aspiration biopsy of axillary lymph node for early breast cancer: implication for axillary surgical stage.

OBJECTIVES: To investigate the value of conventional ultrasonography (US) combined with quantitative shear wave elastography (SWE) in evaluating and identifying target axillary lymph node (TALN) for fine needle aspiration biopsy (FNAB) of patients with early breast cancer. MATERIALS AND METHODS: A total of 222 patients with 223 ALNs were prospectively recruited from January 2018 to December 2021. All TALNs were evaluated by US, SWE and subsequently underwent FNAB. The diagnostic performances of US, SWE, UEor (either US or SWE was positive) and UEand (both US and SWE were positive), and FNAB guided by the above four methods for evaluating ALN status were assessed using receiver operator characteristic curve (ROC) analyses. Univariate and multivariate logistic regression analyses used to determine the independent predictors of axillary burden. RESULTS: The area under the ROC curve (AUC) for diagnosing ALNs using conventional US and SWE were 0.69 and 0.66, respectively, with sensitivities of 78.00% and 65.00% and specificities of 60.98% and 66.67%. The combined method, UEor, demonstrated significantly improved sensitivity of 86.00% (p < 0.001 when compared with US and SWE alone). The AUC of the UEor-guided FNAB [0.85 (95% CI, 0.80-0.90)] was significantly higher than that of US-guided FNAB [0.83 (95% CI, 0.78-0.88), p = 0.042], SWE-guided FNAB [0.79 (95% CI, 0.72-0.84), p = 0.001], and UEand-guided FNAB [0.77 (95% CI, 0.71-0.82), p < 0.001]. Multivariate logistic regression showed that FNAB and number of suspicious ALNs were found independent predictors of axillary burden in patients with early breast cancer. CONCLUSION: The UEor had superior sensitivity compared to US or SWE alone in ALN diagnosis. The UEor-guided FNAB achieved a lower false-negative rate compared to FNAB guided solely by US or SWE, which may be a promising tool for the preoperative diagnosis of ALNs in early breast cancer, and had the potential implication for the selection of axillary surgical modality.

In Situ Growth of Functional Hydrogel Coatings by a Reactive Polyurethane for Biomedical Devices.

Surface modification of thermoplastic polyurethane (TPU) could significantly enhance its suitability for biomedical devices and public health products. Nevertheless, customized modification of polyurethane surfaces with robust interfacial bonding and diverse functions via a simple method remains an enormous challenge. Herein, a novel thermoplastic polyurethane with a photoinitiated benzophenone unit (BPTPU) is designed and synthesized, which can directly grow functional hydrogel coating on polyurethane (PU) in situ by initiating polymerization of diverse monomers under ultraviolet irradiation, without the involvement of organic solvent. The resulting coating not only exhibits tissue-like softness, controllable thickness, lubrication, and robust adhesion strength but also provides customized functions (i.e., antifouling, stimuli-responsive, antibacterial, and fluorescence emission) to the original passive polymer substrates. Importantly, BPTPU can be blended with commercial TPU to produce the BPTPU-based tube by an extruder. Only a trace amount of BPTPU can endow the tube with good photoinitiated capacity. As a proof of concept, the hydrophilic hydrogel-coated BPTPU is shown to mitigate foreign body response in vivo and prevent thrombus formation in rat blood circulation without anticoagulants in vitro. This work offers a new strategy to guide the design of functional polyurethane, an elastomer-hydrogel composite, and holds great prospects for clinical translation.

Effect of dissolved organic matter on selective oxidation of toluene by ozone micro-nano bubble water.

The oxidation capacity of ozone micro-nano bubble water (OMBW) was always higher than ozonated water due to enhanced contact by bubble interface, while the effect of coexisted dissolved organic matter (DOM) on the oxidation efficiency was still unclear. In this paper, batch experiments were carried out to investigate the selective oxidation of toluene by both OMBW and ozonated water (OW) with coexisted DOM in water. Five types of background solutions were applied in this study, including humic acid solution, fulvic acid solution and three types of diluted landfill leachates at the same content of total organic carbon. Results showed that coexisted DOM had a greater inhibition effect on toluene oxidation rate by OMBW, and the oxidation rate of toluene by OMBW and OW became close. It was mainly caused by the decreased reaction rate between toluene and hydroxyl radical (kT-OH·) in OMBW after the introduction of DOM, which competed for the adsorption sites on micro-nano bubble interface. The fraction of ozone to oxidize toluene as well as kT-OH· was in positive correlations with SUVA254 and the content of humic acid-like substances, but negatively correlated with E2/E3, content of tryptophan-like proteins and content of fulvic acid-like substances. In addition, increasing the ozone dose was not effective in increasing the utilization rate of ozone in OMBW due to limited adsorption sites on micro-nano bubble interface. The paper was conductive to the application of ozone micro-nano bubble water in groundwater remediation with complex water matrices.

Does Mammotome biopsy affect surgery option and margin status of breast conserving surgery in breast cancer?

BACKGROUND: The Mammotome, an image-guided, usually ultrasound-guided vacuum-assisted breast biopsy (US-VABB) system, has been widely used in the early diagnosis of breast disease and the complete excision of benign lesions. However, in some malignant lesions underestimated by U.S., whether Mammotome biopsy would affect the surgery option, especially the margin status in breast-conserving surgery (BCS), has never been studied. METHODS: Between 2015 and 2019, 198 patients with 200 lesions who have been diagnosed with breast cancer by Mammotome elsewhere received surgery by pathological confirmation in our center. The clinicopathological characteristics, surgery options, therapies, and the details of the specimen, such as margin status of BCS, tumor residual after VABB, and hematoma were reviewed. RESULTS: Among 200 lesions, 90% were evaluated below US-BIRADS 4b before Mammotome biopsy and 94.5% with a tumor size ≤3 cm. 131 patients received mastectomy (66.2%) and 67 received BCS (33.8%). Hematoma and tumor residual were observed in 37.5% and 71.5% of all lesions, respectively. There is a higher incidence of hematoma in the mastectomy group than in the BCS group (44.4% vs. 23.9%, P=0.005). In BCS group, the positive margin was found in 7 patients at first examination including four focals with re-excision, two extensive with mastectomy and one focal but refusing further surgery. The ultimate success rate of BCS was 95.5%. Margin positivity correlated with tumor residual (P=0.044) but not with hematoma. CONCLUSIONS: Mammotome biopsy might lead to hematoma and tumor residual; however, it is not the determinant factor for a surgery option, and BCS is feasible through a complete excision of tumor residual to acquire negative margin.

Theoretical Study on a Nitrogen-Doped Graphene Nanoribbon with Edge Defects as the Electrocatalyst for Oxygen Reduction Reaction.

Both theory and experiment show that sp2 carbon nanomaterials doped with N have great potential as high-efficiency catalysts for oxygen reduction reactions (ORR). At present, there are theoretical studies that believe that C-sites with positive charge or high-spin density values have higher adsorption capacity, but there are always some counter examples, such as the N-doped graphene nanoribbons with edge defects (ND-GNR) of this paper. In this study, the ORR mechanism of ND-GNR was studied by density functional theory (DFT) calculation, and then the carbon ring resonance energy was analyzed from the perspective of chemical graph theory to elucidate the cause and distribution of active sites in ND-GNR. Finally, it was found that the overpotential of the model can be adjusted by changing the width of the model or dopant atoms while still ensuring proper adsorption energy (between 0.5 and 2.0 eV). The minimum overpotential for these models is approximately 0.36 V. These findings could serve as guidelines for the construction of efficient ORR carbon nanomaterial catalysts.

Comprehensive analysis of the NME gene family functions in breast cancer.

BACKGROUND: An increasing amount of research over recent years on the anti-metastasis function of the non-metastatic (NME) gene family has been challenged, with some studies identifying its involvement in the promotion of oncogenesis. Therefore, the specific functions of the NME gene family require redefining through a comprehensive analysis of tumor heterogeneity and survival benefit. However, the functions of NME genes have not been comprehensively investigated in breast cancer (BC). METHODS: In this study, ONCOMINE, GEPIA, Kaplan-Meier plotter, cBioPortal, String, and metascape databases were utilized for comparison of the mRNA expression, patient survival and network analysis of NME-associated signaling pathways in BC patients. RESULTS: The mRNA expression of NME1 and NME2 was significantly increased in BC. Additionally, high NME 1 and NME2 levels were related to poor overall survival (OS), while the upregulated expression of NME3, NME5, and NME7 indicated prolonged survival. Moreover, increased mRNA level, amplification, or deep deletions in the NME gene family were identified in approximately 41% (450/1098) of all included BC specimens. NME1 and NME2 genes displayed the highest correlation with genetic correlations of the human NME genes in BC. The following pathways were regulated by NME gene upregulation: R-HAS-380270: Recruitment of mitotic centrosome and complexes; GO:0006228: UTP biosynthetic process; R-HAS-380259: Loss of NlP from mitotic centrosomes; hsa03410: Base excision repair; and CORUM:3714: Pericenrin-GCP complex, which was significantly modulated by changes influencing the NME genes. CONCLUSIONS: Collectively, our findings revealed that the elevated expression of NME1 and NME2 could act as a biomarker and predictive tool for BC patients with poor prognosis. Furthermore, our findings indicated that NME3, NME5, and NME7 might play the roles of tumor suppressor genes, which require validation through further experiments.

Pedicled descending branch latissimus dorsi mini-flap in repairing partial mastectomy defect: Shoulder functional and esthetic outcomes.

BACKGROUND: The axillary-approach pedicled descending branch latissimus dorsi (LD) mini-flap presents clear benefits in repairing partial mastectomy defects. This study assessed the functional and esthetic outcomes of this flap compared with conventional breast-conserving surgery (BCS). METHODS: From October of 2015 to March of 2017, patients with early breast cancer were enrolled and assigned to the LD group or conventional BCS (CCS) group according to the need of using the pedicled descending branch LD mini-flap for volume replacement. Muscle strength and range of motion (ROMs) of bilateral shoulders, a disabilities of the arm, shoulder and hand (DASH) questionnaire, and an esthetic evaluation were conducted in all patients at 1 year after surgery. RESULTS: Thirty-two patients were assigned in the LD group, and 28 in the CCS group. There was no significant difference in muscle strength, ROMs of the shoulder or DASH scores between LD and CCS groups. The results of esthetic survey also revealed a similarly high level of esthetics in both groups. Donor-site seroma occurred in three patients in the LD group, and no other complication was observed. CONCLUSIONS: The pedicled descending branch LD mini-flap enabled larger excision with favorable esthetics, minimal functional impairment, low rate of complications, and high level of satisfaction.

Inducing or Preventing Subsequent Malignancies for Breast Cancer Survivors? Double-edged Sword of Estrogen Receptor and Progesterone Receptor.

INTRODUCTION: Hormone receptor and human epidermal growth factor receptor 2 (HER2) status is important for breast cancer (BC) treatment. Previous studies have shown that the long-term treatment outcomes of BC are significantly impaired by the development of subsequent malignancies. Therefore, in the present study, we evaluated the effect of hormone receptor/HER2 status on subsequent malignancies in breast cancer survivors. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results*Stat database (8.3.4) was used as the data source. We identified 535,941 female survivors with first primary BC through the database from 1973 to 2013. Of these patients, 23,964 had developed subsequent contralateral BC, 8398 had developed subsequent uterine or ovarian cancer, and 7435 patients had developed subsequent colorectal cancer. RESULTS: Estrogen receptor (ER) positivity and progesterone receptor (PR) positivity were significant protective factors against subsequent BC and ovarian cancer. However, ER+ BC and PR+ BC were significant risk factors for subsequent colorectal cancer. In addition, HER2+ status demonstrated a marginally significant risk effect for subsequent thyroid cancer. Triple-negative (ER-/PR-/HER2-) status showed elevated risk of subsequent breast, ovarian, and uterine cancer. CONCLUSION: ER+/PR+ patients were less likely develop secondary breast and ovarian malignancies, possibly owing to advancements in anti-ER/PR treatment. However, ER+/PR+ patients were more likely to develop colorectal cancer, suggesting a potential screening necessity for these patients.

A Novel Displacement and Tilt Detection Method Using Passive UHF RFID Technology.

The displacement and tilt angle of an object are useful information for wireless monitoring applications. In this paper, a low-cost detection method based on passive radio frequency identification (RFID) technology is proposed. This method uses a standard ultrahigh-frequency (UHF) RFID reader to measure the phase variation of the tag response and detect the displacement and tilt angle of RFID tags attached to the targeted object. An accurate displacement result can be detected by the RFID system with a linearly polarized (LP) reader antenna. Based on the displacement results, an accurate tilt angle can also be detected by the RFID system with a circularly polarized (CP) reader antenna, which has been proved to have a linear relationship with the phase parameter of the tag’s backscattered wave. As far as accuracy is concerned, the mean absolute error (MAE) of displacement is less than 2 mm and the MAE of the tilt angle is less than 2.5° for an RFID system with 500 mm working range.

Pedicled Descending Branch Latissimus Dorsi Mini-flap for Repairing Partial Mastectomy Defect: A New Technique.

Volume loss is 1 of the major factors influencing cosmetic outcomes of breast after partial mastectomy (PM), especially for smaller breasts, and therefore, volume replacement is critical for optimizing the final aesthetic outcome. We present a novel technique of raising a pedicled descending branch latissimus dorsi (LD) mini-flap for reconstruction of PM defects via an axillary incision. After PM, the LD mini-flap is harvested through the existing axillary incision of the axillary dissection or the sentinel lymph node biopsy. The descending branches of thoracodorsal vessels and nerve are carefully identified and isolated. The transverse branches are protected to maintain muscle innervation and function. The LD muscle is then undermined posteriorly and inferiorly to create a submuscular pocket and a subcutaneous pocket between LD muscle and superficial fascia. Once the submuscular plane is created, the muscle is divided along the muscle fibers from the deep surface including a layer of fat above the muscle. Finally, the LD mini-flap is transferred to the breast defect. Given the limited length and mobility of the LD mini-flap, this approach is best utilized for lateral breast defects. However, for medial defects, the lateral breast tissue is rearranged to reconstruct the medial breast defect, and an LD mini-flap is then used to reconstruct the lateral breast donor site. This technique can therefore be employed to reconstruct all quadrants of the breast and can provide aesthetic outcomes without scars on the back, with minimal dysfunction of LD muscle.

Survival outcomes of patients with lobular carcinoma in situ who underwent bilateral mastectomy or partial mastectomy.

AIM: To compare the survival outcomes between patients treated with bilateral mastectomy and partial mastectomy alone as the initial surgical management for primary lobular carcinoma in situ (LCIS). PATIENTS AND METHODS: Patients with histologically confirmed LCIS underwent partial mastectomy alone or bilateral mastectomy were identified by the SEER*Stat database (version 8.3.2) released in 2016. The primary outcome measure was all-cause mortality and the secondary outcome measure was breast cancer-specific mortality. RESULTS: Of the 5964 cases included in the analysis, 208 cases underwent bilateral mastectomy and 5756 cases underwent partial mastectomy alone. The 1-, 5- and 10-year estimated overall survival rates were 99.7%, 96.7% and 91.7%, respectively. Univariate and multivariate proportional hazards regression (Cox) analyses showed no significant difference between the risk of all-cause mortality in the bilateral mastectomy group compared with the partial mastectomy group (HR = 1.106, 95% confidence interval [CI] 0.350-3.500, P = 0.86). In propensity score-matched model, bilateral mastectomy still did not show benefit to overall mortality (HR = 2.248, 95% CI 0.451-11.200). Patients older than 60 years of age showed a higher risk of all-cause mortality (HR = 7.593, 95% CI 5.357-10.764, P < 0.0001). No risk factors, including surgery type, were identified for breast cancer-specific survival. CONCLUSIONS: Survival outcomes of patients with LCIS who underwent partial mastectomy without radiotherapy were not inferior to patients who underwent bilateral prophylactic mastectomy. Breast cancer-specific mortality in patients with LCIS was extremely low; aggressive prophylactic surgery like bilateral prophylactic mastectomy should not be advocated for most patients with LCIS.

The effect of preoperative serum triglycerides and high-density lipoprotein-cholesterol levels on the prognosis of breast cancer.

OBJECTIVES: Although dyslipidemia has been documented to be associated with several types of cancer including breast cancer, it remains uncertainty the prognostic value of serum lipid in breast cancer. The purpose of this study is to evaluate the association between the preoperative plasma lipid profile and the prognostic of breast cancer patients. METHODS: The levels of preoperative serum lipid profile (including cholesterol [CHO], Triglycerides [TG], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoAI], and apolipoprotein B [ApoB]) and the clinical data were retrospectively collected and reviewed in 1044 breast cancer patients undergoing operation. Kaplan-Meier method and the Cox proportional hazards regression model were used in analyzing the overall survival [OS] and disease-free survival [DFS]. RESULTS: Combining the receiver-operating characteristic and Kaplan-Meier analysis, we found that preoperative lower TG and HDL-C level were risk factors of breast cancer patients. In multivariate analyses, a decreased HDL-C level showed significant association with worse OS (HR: 0.528; 95% CI: 0.302-0.923; P = 0.025), whereas a decreased TG level showed significant association with worse DFS (HR: 0.569; 95% CI: 0.370-0.873; P = 0.010). CONCLUSIONS: Preoperative serum levels of TG and HDL-C may be independent factor to predict outcome in breast cancer patient.

Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing.

Hereditary cancers occur because of inherited gene mutations. Genetic testing has been approved to provide information for risk assessment and rationale for appropriate intervention. Testing methods currently available for clinical use have some limitations, including sensitivity and testing throughput, etc. Next generation sequencing (NGS) has been rapidly evolving to increase testing sensitivity and throughput. It can be potentially used to identify inherited mutation in clinical diagnostic setting. Here we develop an effective method employing target enrichment and NGS platform to detect common as well as rare mutations for all common hereditary cancers in a single assay. Single base substitution across 115 hereditary cancer related genes using YH (the first Asian genome) was characterized to validate our method. Sensitivity, specificity and accuracy of 93.66, 99.98 and 99.97 %, were achieved, respectively. In addition, we correctly identified 53 SNVs and indels of BRCA1 and BRCA2 in two breast cancer specimens, all confirmed by Sanger sequencing. Accuracy in detecting copy number variation (CNV) was corroborated in 4 breast cancer specimens with known CNVs in BRAC1. Application of the method to 85 clinical cases revealed 22 deleterious mutations, 11 of which were novel. In summary, our studies demonstrate that the target enrichment combined with NGS method provides the accuracy, sensitivity, and high throughput for genetic testing for patients with high risk of hereditary or familial cancer.

Breast-conserving therapy: a viable option for young women with early breast cancer--evidence from a prospective study.

BACKGROUND: This study evaluated the security of breast-conserving treatment (BCT) in young patients and the effect of regional radiation therapy on young patients with 1-3 positive nodes (N+) treated with BCT. METHODS: In this prospective concurrent controlled study, 164 patients were defined as the BCT group, and regional radiation therapy was delivered to patients with 1-3 N+. Modified radical mastectomies (MRMs) were performed on 224 patients without regional radiation therapy. RESULTS: The 9-year local recurrence (LR) rate of the BCT was 7 %, compared with 3 % in the MRM group (p = 0.055). The 9-year regional recurrence (RR) rate was 6 % for the BCT group and 12 % for the MRM group (p = 0.048). The distant metastasis (DM)-free and breast cancer-specific survival rates were similar between the two groups. RR was an independent prognostic factor for DM [hazard ratio 3.27; 95 % confidence interval (CI) 1.726-6.208] and breast cancer-specific survival (hazard ratio 5.814; 95 % CI 2.690-12.568), whereas LR was not an independent prognostic factor for DM or breast cancer-specific survival. CONCLUSIONS: Young patients treated with BCT have a higher LR rate than that of MRM. However, LR has no detrimental effect on DM-free and breast cancer-specific survival rates, whereas RR is a strong risk factor of DM and death. Regional radiation therapy for young patients with 1-3 N+ may reduce RR and improve survival rates.

Signet-ring cell carcinoma of the breast: a case report.

Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under 'mucin-producing carcinomas' and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.

Targeted expression of miR-34a using the T-VISA system suppresses breast cancer cell growth and invasion.

Recurrence and metastasis result in a poor prognosis for breast cancer patients. Recent studies have demonstrated that microRNAs (miRNAs) play vital roles in the development and metastasis of breast cancer. In this study, we investigated the therapeutic potential of miR-34a in breast cancer. We found that miR-34a is downregulated in breast cancer cell lines and tissues, compared with normal cell lines and the adjacent nontumor tissues, respectively. To explore the therapeutic potential of miR-34a, we designed a targeted miR-34a expression plasmid (T-VISA-miR-34a) using the T-VISA system, and evaluated its antitumor effects, efficacy, mechanism of action, and systemic toxicity. T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed breast cancer cell growth, migration, and invasion in vitro by downregulating the protein expression levels of the miR-34a target genes E2F3, CD44, and SIRT1. In an orthotopic mouse model of breast cancer, intravenous injection of T-VISA-miR-34a:liposomal complex nanoparticles significantly inhibited tumor growth, prolonged survival, and did not induce systemic toxicity. In conclusion, T-VISA-miR-34a lead to robust, specific overexpression of miR-34a in breast cancer cells and induced potent antitumor effects in vitro and in vivo. T-VISA-miR-34a may provide a potentially useful, specific, and safe-targeted therapeutic approach for breast cancer.

A case report of primary small cell carcinoma of the breast and review of the literature.

Primary small cell carcinoma (SCC) of the breast, an exceedingly rare and aggressive tumor, is often characterized by rapid progression and poor prognosis. We report a case of primary SCC of the breast that was diagnosed through pathologic and immunohistochemical examinations. Computed tomography (CT) scans failed to reveal a non-mammary primary site. Due to the scant number of relevant case summaries, this type of tumor is proved to be a diagnostic and therapeutic challenge. Therefore, we also reviewed relevant literature to share expertise in diagnosis, clinicopathologic characteristics, treatment, and prognosis of this type of tumor. Future studies with more cases are required to define more appropriate treatment indications for this disease.

Absence of evidence for epidermal growth factor receptor and human homolog of the Kirsten rat sarcoma-2 virus oncogene mutations in breast cancer.

AIMS: The epidermal growth factor receptor (EGFR) is an available target of effective anti-EGFR therapy for human breast cancer. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a main downstream signaling molecule in the EGFR pathway. The aim of this study was to assess the presence of EGFR and KRAS gene mutations in breast cancer. MATERIALS AND METHODS: EGFR and KRAS gene mutations were investigated in formalin-fixed, paraffin-embedded tissues from 143 Chinese female patients with breast cancer by means of real-time quantitative polymerase chain reaction (RT-PCR). RESULTS: Based on RT-PCR, 2/143 (1.4%) samples and 1/143 (0.7%) had EGFR and KRAS gene mutations, respectively. Overall, none of the cases was identified with mutations of both of these two genes. CONCLUSIONS: In this study, both EGFR and KRAS mutations were present rarely in this cohort of samples with breast cancer. This suggested that mutation analyses for EGFR and KRAS are not useful as screening tests for sensitivity to anti-EGFR therapy for breast carcinomas.

Targeted expression of Escherichia coli purine nucleoside phosphorylase and Fludara® for prostate cancer therapy.

BACKGROUND: Previous studies have shown that Herpes Simplex Virus thymidine kinase (HSV-tk)/ganciclovir (GCV) comprised the most commonly used suicide gene therapy for prostate cancer, with modest results being obtained. However, novel suicide genes, such as Escherichia coli purine nucleoside phosphorylase (PNP), have been utilized to demonstrate more potent tumor killing and an enhanced bystander effect on local, non-expressing cells compared to HSV-tk. METHODS: PNP/fludarabine (Fludara®; fludarabine phosphate; Berlex Labs, Richmond, CA, USA) was deliveried by prostate-specific, rat probasin-based promoter, ARR2PB. After infection of various cell lines with ADV.ARR(2) PB-PNP and administration of androgen analog, R1881, expression of PNP mRNA was detected; in vivo, the antitumor effect of the ARR(2) PB-PNP/Fludara system was monitored and analyzed, as well as animal survival. RESULTS: After in vitro infection with ADV.ARR(2) PB-PNP (multiplicity of infection = 10), LNCaP cells were more sensitive to a lower concentration Fludara (LD(50) , approximately 0.1 µg/ml) in the presence of R1881. Furthermore, robust bystander effects after R1881/Fludara treatment were observed in LNCaP cells after infection with bicistronic vector ADV.ARR2PB/PNP-IRES-EGFP in contrast to a much weaker effect in cells treated with ADV.CMV-HSV-tk/GCV. In vivo, tumor size in the ADV.ARR2PB-PNP/Fludara treatment group was dramatically smaller than in the control groups, and the mice treated with our system had a significantly prolonged survival, with three of eight mice surviving up to the 160-day termination point, as well as no systemic toxicity. CONCLUSIONS: The ARR(2) PB-PNP/Fludara system induced massive tumor cell death and a prolonged life span without systemic cytotoxicity; therefore, it might be a more attractive strategy for suicide gene therapy of prostate cancer.