Frequency of periprocedural myocardial injury and infarction stratified by cardiac troponin I and cardiac troponin T.

BACKGROUND: There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI. OBJECTIVES: This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina. RESULTS: Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34 %, 2.05 %, and 4.94 % respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84 % vs. 1.91 %, p < 0.001; ARC 2: 3.15 % vs. 1.56 %, p = 0.136; and 4UDMI 5.91 % vs. 4.51 %, p = 0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31 % and 27.10 % of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29 % vs. 53.47 %, p < 0.001, Major: 49.21 % vs. 17.36 %, p < 0.001). CONCLUSIONS: Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI.

Identification of knowledge anxiety factors among researchers based on grounded theory.

Based on a grounded theoretical analysis of interviews and open data, this study develops a model delineating the factors influencing Knowledge Anxiety, encompassing 5 primary categories and 20 subcategories. These categories encompass Academic Characteristics (knowledge quantity, knowledge quality, and knowledge content), Outer Environment (paid marketing, negative feedback, intense competition, and evaluation mechanism), and Cognitive Environment (work stress, scientific research funding, interpersonal relationships, Time limitation, and Cause difficult) which have been identified as external drivers influencing researchers' Knowledge Anxiety. Conversely, Ability Characteristics (scientific literacy, personality traits, English proficiency, and self-expectations) and Emotional Cognition (inertia thinking, negative self-concept, perceived risks, self-efficacy, and knowledge demand) have been recognized as internal drivers impacting researchers' Knowledge Anxiety. Findings reveal that external factors such as Academic Characteristics, Outer Environment, and Cognitive Environment directly impact researchers' susceptibility to Knowledge Anxiety. Internal factors, represented by Individual Competencies and Emotional Perception, also wield significant influence. Furthermore, external forces can affect Knowledge Anxiety either directly or indirectly by interfacing with internal determinants. This study underscores that researchers' Knowledge Anxiety emerges from intricate interactions among diverse factors, rather than stemming from a solitary cause. These insights furnish valuable comprehension and prospective strategies for mitigating Knowledge Anxiety among researchers, ultimately contributing to the advancement of research in this domain.

Immunogenicity and safety of SARS-CoV-2 vaccine in hemodialysis patients: A systematic review and meta-analysis.

Rationale and objective: COVID-19 vaccination is the most effective way to prevent COVID-19. For chronic kidney disease patients on long-term dialysis, there is a lack of evidence on the pros and cons of COVID-19 vaccination. This study was conducted to investigate the immunogenicity and safety of COVID-19 vaccines in patients on dialysis. Methods: PubMed, MEDLINE, EMBASE, and the Cochrane Library were systemically searched for cohort, randomized controlled trials (RCTs), and cross-sectional studies. Data on immunogenicity rate, antibody titer, survival rate, new infection rate, adverse events, type of vaccine, and patient characteristics such as age, sex, dialysis vintage, immunosuppression rate, and prevalence of diabetes were extracted and analyzed using REVMAN 5.4 and Stata software. A random effects meta-analysis was used to perform the study. Results: We screened 191 records and included 38 studies regarding 5,628 participants. The overall immunogenicity of dialysis patients was 87% (95% CI, 84-89%). The vaccine response rate was 85.1 in hemodialysis patients (HDPs) (1,201 of 1,412) and 97.4% in healthy controls (862 of 885). The serological positivity rate was 82.9% (777 of 937) in infection-naive individuals and 98.4% (570 of 579) in patients with previous infection. The Standard Mean Difference (SMD) of antibody titers in dialysis patients with or without previous COVID-19 infection was 1.14 (95% CI, 0.68-1.61). Subgroup analysis showed that the immunosuppression rate was an influential factor affecting the immunogenicity rate (P < 0.0001). Nine studies reported safety indices, among which four local adverse events and seven system adverse events were documented. Conclusions: Vaccination helped dialysis patients achieve effective humoral immunity, with an overall immune efficiency of 87.5%. Dialysis patients may experience various adverse events after vaccination; however, the incidence of malignant events is very low, and no reports of death or acute renal failure after vaccination are available, indicating that vaccine regimens may be necessary. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42022342565, identifier: CRD42022342565.

A review of Cystoderma (Agaricales/Basidiomycota) from China with four new species and two new records.

Cystoderma comprises the species with heavily universal veil remnants on basidiomes, weakly to strongly amyloid basidiospores, evanescent floccose-scaly ring zone or persistent membranous ring, which were often encountered in forests and grassland. However, they were less studied than other mushroom groups mainly because of its unclearly phylogenetic position. In this study, we gathered 16 specimens from Southwest and Northwest China, where were the richest biodiversity areas in China, and produced their ITS and nrLSU sequences. The related morphological examinations and molecular phylogenetic analysis showed they belonged to eight species, of which four were new species, and named as Cystoderma lilaceum, C. pseudoamianthinum, C. rugosolateritium, C. subglobisporum, and of which two were new records from China, and they were C. granosum, C. subvinaceum. New species and new records were described in details and discussed with other species. This study not only showed the novel geographical distributions as well as high species diversity of Cystoderma in China, but also provided more research data for the further studies in mushrooms systematics.

Retard or exacerbate: Role of long non-coding RNA growth arrest-specific 5 in the fibrosis.

Fibrosis is the endpoint of pathological remodeling involving different expressions of non-coding RNA(ncRNA) including long non-coding RNA growth arrest-specific 5 (lncRNA Gas5). Up to now, many studies have demonstrated that lncRNA Gas5 may play a vital regulatory role in the occurrence and development of organ fibrosis including liver, renal and cardiac fibrosis et al. Furthermore, Gas5 may also serve as a biomarker in diagnostic settings for fibrosis diseases. Structurally, IncRNA Gas5 impacts fibrosis via its distinct structural modules. In response to various external stresses, distinct functional complexes on different parts of Gas5 sequence influence cell proliferation and survival, thus affecting the inflammatory process and deposition of extracellular matrix(ECM) in organ fibrosis. However, there is no consensus on the role of Gas5 in fibrosis and its changed expression under various circumstances. In this review, we present an overview of what is known about the effect of Gas5 in organ fibrosis so far and for the first time explain its mechanism in the progression of fibrosis based on its unique structure.

The relationship analysis and reaction mechanism of carbon, nitrogen, and phosphorus metabolism in sewage treatment in plateau habitat.

The efficiency of pollutant removal in sewage is mainly determined by the structure and abundance of microbial flora, which is essentially represented by the type and abundance of genes and enzymes, and the reaction mechanism is the abundance and degree of reaction of metabolic pathways and metabolic modules. In order to study the mechanism of carbon, nitrogen, and phosphorus metabolism of activated sludge microflora in the A2O process at high altitudes at different temperatures, so as to improve the removal rate of pollutants and reduce the discharge concentration of pollutants. Based on the research environment of high-altitude environmental research, the author used the A2O system as the treatment process and put Illumina MiSeq high-through sequencing technology to comprehensively dissect the reaction relationship of carbon, nitrogen and phosphorus metabolic pathways, and derived the main functional genes and enzymes of carbon, nitrogen, and phosphorus metabolism. It was demonstrated that the abundance of the most metabolic modules and functional genes tended to increase and then decrease with increasing temperature. In particular, the highest abundance and activity and the best pollutant removal efficiency were observed at 20 °C. This study will provide a valuable reference for the study of carbon metabolism, nitrogen metabolism, and phosphorus metabolism of microbial flora in sewage treatment under plateau habitats.

Egg, cholesterol and protein intake and incident type 2 diabetes mellitus: Results of repeated measurements from a prospective cohort study.

BACKGROUND & AIMS: Epidemiological evidence on the associations of egg, cholesterol and protein intake with risk of type 2 diabetes is inconsistent. Therefore, we conducted this study to explore these associations among Chinese adults. METHODS: Data from 4 waves (2004, 2006, 2009 and 2011) of the China Health and Nutrition Survey were used. A multistage random-cluster sampling method was employed to recruit the participants in both rural and urban areas. We included individuals who participated in 2004 and any waves afterwards. Those 1) below 18 years of age; 2) with diabetes at baseline; or 3) with extreme energy intake (men: <800 kcal or >6000 kcal; women: <600 kcal or >4000 kcal) were excluded. Respondents were classified into four groups according to quartiles of egg, cholesterol and protein intake per day. Numbers of eggs per day were calculated by dividing egg intake in grams by 50 g. Diagnosis of type 2 diabetes was self-reported. Logistic generalized estimation equation models were employed. RESULTS: There were 7312 individuals included in 2004, 6390 in 2006, 4826 in 2009 and 4963 in 2011. The mean age of participants at baseline was 48.3 years and 47.2% were men. Over an average of 5.8-y follow-up, 209 developed type 2 diabetes. After adjustment for demographic, lifestyle and dietary confounders, the odds ratio of type 2 diabetes for those in the highest compared with the lowest protein intake quartile was 2.38 (95% CI: 1.43, 3.98). The odds ratio of individuals with ≥3 eggs/day versus none was 3.76 (95% CI, 2.05, 6.90). Cholesterol intake was not associated with type 2 diabetes. CONCLUSIONS: Individuals with the highest protein intake had over a 2-fold increased risk of type 2 diabetes compared with those with the lowest protein intake. A high intake of egg, but not dietary cholesterol, was associated with type 2 diabetes. This association warrants further investigation.

Recent advances in intermolecular 1,2-difunctionalization of alkenes involving trifluoromethylthiolation.

Trifluoromethylthiolative difunctionalization of alkenes, a cheap and abundant feedstock, which installs a trifluoromethylthiol (SCF3) group and another unique functional group across the carbon-carbon double bonds, provides an ideal strategy for the preparation of ß-functionalized alkyl trifluoromethyl sulfides and has become a hot topic recently. This review aims to summarize the major progress in this exciting research area, with particular emphasis on the mechanistic aspects of the reaction pathways.

Pancreatic acinar cell carcinoma-case report and literature review.

BACKGROUND: Pancreatic acinar cell carcinoma (ACC) is a rare tumor that constitutes 1% of all pancreatic neoplasms. Pancreatic ACC has unique characteristics in terms of biological behavior, imaging and prognosis. CASE PRESENTATION: The present study reported two cases of pancreatic ACC confirmed by postoperative pathology and both cases exhibited several different imaging features and laboratory test results. Both cases had approximately 4 cm mass located in uncinate process of pancreas. Dilated intra- and extra-hepatic bile ducts was observed in one case, along with calcification. Heterogeneous enhancement of the tumor was exhibited in both patients with different intensities. Obstructive jaundice, elevated α-fetoprotein and CA 19-9 was found in one case, while the other case had normal liver function and tumor markers. CONCLUSIONS: It was difficult to accurately diagnose pancreatic ACC before the operation despite its unique characteristics. Radical resection was the best treatment modality for resectable pancreatic ACC.

Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat.

Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo.

A new species of Agaricus section Minores from China.

Agaricus gemloides sp. nov. is characterised by its reddish brown fibrillose squamose on the pileus, relatively slender basidiome and broader basidiospores. In this article, it is introduced based on its distinguished morphological features and molecular phylogenetic position.

Two-phase integrated sludge thickening and digestion (TISTD) reactor microbial diversity and community structure succession rules.

A two-phase integrated sludge thickening and digestion (TISTD) reactor composed of an inner and an outer reactor was developed. Acidification of natural organic material was the primary process in the outer reactor, whilst methane production was the dominant bioreaction occurring in the inner one. The special structure of TISTD thus enables the effective separation of the acid production phase and methane production phase during sludge processing. Molecular biological technology, including 16S rRNA gene and PCR-TGGE, was utilized to investigate the overall microbial community structure and diversity, as well as the processes of dynamic change. Analysis was also conducted on succinate dehydrogenase and coenzyme F420 change trends at each dosing ratio. The microbial community structure of the system exhibited disorder gradually and led to collapse when the dosing ratio increased above 30 %.

Birth weight and lung function in a cohort of Chinese school children.

OBJECTIVE: Evidence on the association between birth weight and lung function is conflicting. We evaluated the children's lung function in relation to their birth weight in China. METHODS: A prospective cohort study was conducted in 1,599 school children. Baseline data on birth weight and other potential confounding variables were obtained from self-administered questionnaires. Pulmonary function tests were performed with a standard procedure and repeated 6 months later. RESULTS: There were no significant differences in the standard deviation score (SDS) of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) between children with low birth weight (LBW) and those with normal birth weight (NBW). The growth rates in lung function between children with LBW and NBW were also insignificant. CONCLUSIONS: No association between birth weight and lung function was found among Chinese school children.

Microarray reveals complement components are regulated in the serum-deprived rat retinal ganglion cell line.

PURPOSE: Glaucoma is a progressive eye disease that leads to blindness due to loss of retinal ganglion cells (RGCs). There are difficulties in using primary cultures of purified RGC to study this pathophysiology. RGC-5, a transformed not RGC line, expresses several markers characteristic of the RGCs. The aim of this study was to generate a genome-wide gene expression of RGC-5 following serum deprivation and to identify candidate genes that may be involved in the signal transduction pathways. METHODS: Apoptosis in the transformed rat RGC-5 was induced by serum deprivation for 0, 8, 24, 48, and 96 h. Briefly, 400 ng of RNA from each sample was reverse transcribed and labeled with Cy3 dye. Fragmented fluorescent cRNA was mixed with hybridization buffer and incubated at 60 degrees C for 16 h. Labeled cRNA was hybridized to Rat Genome Oligonucleotide Arrays. These arrays contain 22,775 transcripts with one oligonucleotide per transcript (60-mer). Gene expression from scanned images was quantified and analyzed using ArrayVision software. Reproducibility among triplicate arrays was determined by ANOVA statistical analysis. Significant differences in gene expression between apoptotic and nonapoptotic cells were determined based on p-values. RESULTS: Of the 22,775 transcripts present on the arrays (Agilent rat genome, 60-mer), 713 (8 h), 1,967 (24 h), 1,011 (48 h), and 1,161 (96 h) were differentially expressed relative to the 0 h time point (p-values <0.05). Twenty-three transcripts were common to 8, 24, 48, and 96 h and 130 transcripts were common to the 24, 48, and 96 h time points. The two most highly upregulated genes were Fdft1 and Lgals3 (8 h), C3 and Fcgrt (24 h), C and Lcn2 (48 h), and Mgp and C3 (96 h). A subset of the differentially expressed genes identified in microarray data (Ftl1, C3, C1s, Neu1, Polr2g, Acadm, Nupr1, Gch, Dia1, DNase1, Tgfb2, and Cyr61) were validated using quantitative real time polymerase chain reaction (QRT-PCR). Here we show that complement factor H (CFH), the major inhibitor of the alternative complement pathway is downregulated in serum-deprived RGC-5. CFH protein was detected within RGC-5 cells as well as the rat retina with the aid of immunocytochemistry and confocal microscopy. CONCLUSIONS: This study was undertaken to generate a genome-wide gene expression profile of RGC-5 after serum deprivation, and to identify candidate and novel genes that may be involved in the signal transduction pathways leading to apoptosis. RGC-5 serum deprivation revealed up-and downregulation in gene expression profiles. The data gathered from this study was the first report that the genes identified in microarray data and validated by real-time RT-PCR may play an important role in RGC-5 cell death. Among the validated genes, C3 and C1s showed significant upregulation of the complement component pathway. The results further indicate that components of the complement pathway are present in neurons of the rat retina. The data indicated that complement factors are likely involved in the pathway leading to ganglion cell death in the serum-deprivation paradigm, which may be similar to the mechanism of cell death in glaucoma.

Biodegradation of gallotannins and ellagitannins.

Nowadays, many researches have been made on gallotannin biodegradation and have gained great success in further utilization. Some of industrial applications of these findings are in the production of tannase, the biotransformation of tannic acid to gallic acid or pyrogallol and detannification of food and fodder. Although ellagitannins have the typical C-C bound which is more difficult to be degraded than gallotannins, concerted efforts are still in progress to improve ellagitannin degradation and utilization. Currently, more attention is mainly focused on intestinal microflora biodegradation of tannins especially ellagitannins which can contribute to the definition of their bioavailability for both human beings and ruminants. Also there have been endeavours to utilize the tannin-degrading activity of different fungi for ellagitannin-rich biomass, which will facilitate application of tannin-degrading enzymes in strategies for improving industrial and livestock production. Due to the complicated structures of complex tannins and condensed tannins, the biodegradation of them is much more difficult and there are fewer researches on them. Therefore, the researches on the mechanisms of gallotannin and ellagitannin biodegradation can result in the overall understanding to the biodegradation of complex tannins and condensed tannins. Biodegradation of tannins is in an incipient stage and further studies have to be carried out to exploit the potential of various tannins for largescale applications in food, fodder, medicine and tannery effluent treatment.

[A dopaminergic projection from the dorsal raphe nucleus to the inner ear].

OBJECTIVE: To investigate the efferent pathway from the dorsal raphe nucleus to the inner ear. METHODS: Eleven adult cats weighing 2.0 - 3.0 kg were used. The animals had no middle-ear disease and their auricle reflex was sensitive to sound. They were divided into experimental group (8 cats) and control group (3 cases). The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunofluorescence technique after a survival period of 7 days. For studying other fluorescence labelling, the sections containing CTB-labelled neurons were divided into four groups and incubated in antisera directed against tyrosine hydroxylase (TH), serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine B-hydroxylase (DBH), respectively. Single-and double-labelled neurons were identified from the DRN. RESULTS: (1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB-labelled neurons were densely distributed in a dorsomedial part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN. Of the total population of CTB-labelled neurons, 100% were TH-labelled neurons (double labelling) and no double-stained neuron with 5-HT, GABA and DBH was observed in the DRN. CONCLUSIONS: There was a projection from DRN to the inner ear and this pathway might be a dopaminergic projection.

C4d as a significant predictor for humoral rejection in renal allografts.

OBJECTIVE: To determine the diagnostic and clinical significance of C4d accumulation in renal allografts followed by acute rejection. METHODS: A total of 158 graft biopsies performed from December 1997 to December 2002 were classified, according to the Banff-97 criteria, into hyperacute rejection (HAR, three cases), acute vascular rejection (AVR, 27), acute cellular rejection (ACR, 24), borderline rejection (BR, 38), acute tubular necrosis (ATN, five), stable graft function (SGF, 30) and baseline kidney (31). Immunohistochemical technique was used to determine the C4d deposition level. RESULTS: The percentages of C4d positive in HAR, AVR, ACR, BR, ATN, SGF and baseline kidney groups were 100% (3/3), 77.8% (21/27), 37.5% (9/24), 23.7% (9/38), 0% (0/5), 3.3% (1/30), 0% (0/31), respectively. In acute rejection patients, the peak serum creatinine (sCr) level in C4d(ptc)-positive group (41 cases) was 334.82 +/- 238.37 micromol/L, with that of C4d(ptc)-negative group (47 cases) being 220.20 +/- 176.94 micromol/L (p < 0.01). After treatment, the trough sCr level in C4d(ptc)-positive group and C4d(ptc)-negative group were 176.87 +/- 111.80 and 121.75 +/- 34.59 micromol/L (p < 0.01), respectively. In each AVR, ACR and BR subgroups, the peak sCr level, the trough sCr level, after 3 or 6 months of AR, the sCr level in C4d(ptc)-positive subgroup was higher than that of C4d(ptc)-negative subgroup. There were more resistance against steroid therapy [65.9% (27/41) vs. 36.2% (17/47), p = 0.005] and a higher rate of graft loss [29.3% (12/41) vs. 6.4% (3/47), p = 0.001] in C4d(ptc)-positive group than those of C4d(ptc)-negative group. In each C4d(ptc)-positive subgroup of AVR, ACR and BR the complete reversion was 57.1, 56 and 66.7%, respectively, it is almost same. CONCLUSION: The C4d deposition level is of great value in diagnosis of acute rejection caused by humoral immune components. It is a significant predictor of graft survival and will be of great help when treating acute rejection.

Prediction of drug sensitivity and drug resistance in cancer by transcriptional and proteomic profiling.

The oncologist's challenges, particularly with advanced cancers, are (a) how to predict tumor response to a given drug or regimen; (b) how to predict which tumors of identical histology will remain indolent and which will be likely to progress; and (c) how to determine the appropriate timing of the emergence of drug-resistant cancer cells and hence switch to appropriate therapy. These issues are still unresolved; current clinical practice is hampered by the complexity and heterogeneity of anti-tumor drug resistance where multiple cellular, tumor microenvironment and host factors operate simultaneously. The rapid accumulation of genomic and proteomic databases for complex biological systems, such as cancer, together with advances in technology platforms, have paved the way to an increased molecular understanding and prediction of antitumor drug response. The complex phenotype of drug resistance can now be dissected and specific, clinically relevant markers pinpointed. Several microarray studies of genetic patterns from untreated and pre-treated cancers have provided "fingerprints" that can predict response to therapeutics. Nevertheless, such approaches require further validation in experimental models and in large clinical trials before their routine clinical use. Moreover, comparative transcriptional profiling alone is unlikely to predict drug sensitivity/resistance, a dynamic process where protein phosphorylation, protein trafficking, and protein-protein interactions with secondary effectors play key roles in the fate of cancer cells following therapeutic stress. Functional proteomics is potentially more predictive, but still faces technical challenges with regards to sampling, tumor heterogeneity, and lack of standardized methodologies. These obstacles are surmountable with current concerted research efforts and availability of powerful high-throughput genomic and proteomic instrumentations, and thus approaches to predict and overcome drug resistance could be rationalized.

The interface between ErbB and non-ErbB receptors in tumor invasion: clinical implications and opportunities for target discovery.

The molecular switches by which malignant cancer cells evolve from a confined to an invasive state are poorly understood, but seem to involve a progressive activation of a signaling network shared by several growth factor receptors and non-receptor molecules. Abnormal expression of ErbB tyrosine kinase receptors, commonly seen in cancer, is an early event in the invasive process, which makes these receptors exciting targets for drug discovery. The past few years have been full of promise for ErbB targeting in the context of receptor overexpression, but also fraught with disappointment as clinical efficacy has often been hampered by potential problems such as the heterogeneity of receptor expression within the same tumor, and the extensive cooperative signaling among ErbB and non-ErbB receptors. Cooperative signaling is a common characteristic of invasive cancer cells, and is believed to dictate the genetic program that controls invasion switches. Molecular studies on the combinatorial signaling involved in tumor invasion are becoming a fertile area for target discovery in cancer. This review discusses how cooperative signaling between ErbB and non-ErbB receptors regulates tumor invasion and hence provides multiple opportunities for drug discovery, and how current therapies and investigational drugs could pave the way to even more potent alternative combinatorial therapeutic approaches for invasive cancers.