Ophiorrhiza mungos-Mediated Silver Nanoparticles as Effective and Reusable Adsorbents for the Removal of Methylene Blue from Water.

Green synthesis of silver nanoparticles (AgNPs) using a plant extract has attracted significant attention in recent years. It is found as an alternative for other physicochemical approaches because of its simplicity, low cost, and eco-friendly rapid steps. In the present study, Ophiorrhiza mungos (Om)-mediated AgNPs have been shown to be effective bioadsorbents for methylene blue (MB) dye removal (88.1 ± 1.74%) just after 1 h at room temperature in the dark from an aqueous medium for the first time. Langmuir and Freundlich isotherms fit the experimental results having the correlation coefficient constants R2 = 0.9956 and R2 = 0.9838, respectively. From the Langmuir fittings, the maximum adsorption capacity and adsorption intensity were found to be 80.451 mg/g and 0.041, respectively, indicating the excellent performance and spontaneity of the process. Taking both models under consideration, interestingly, our findings indicated a fairly cooperative multilayer adsorption that might have been governed by chemisorption and physisorption, whereas the adsorption kinetics followed the pseudo-second-order kinetics mechanism. The positive and low values of enthalpy (ΔH0 = 4.91 kJ/mol) confirmed that adsorption is endothermic and physical in nature; however, the negative free energy and positive entropy value (ΔS0 = 53.69 J/mol K) suggested that the adsorption is spontaneous. The biosynthesized adsorbent was successfully reused up to the fifth cycle. A proposed reaction mechanism for the adsorption process of MB dye onto Om-AgNPs is suggested. The present study may offer a novel finding such as an effective and sustainable approach for the removal of MB dye from water using biosynthesized Om-AgNPs as reusable adsorbents at a comparatively faster rate at a low dose for industrial applications.

Assessing Trace Metal-Based Human Health Risks for Commonly Used Body Soaps in Bangladesh.

In Bangladesh, body soaps are very popular among consumers due to their flavors and low alkali content. The current study assesses the contamination of several trace metals (TMs) such as iron (Fe), copper (Cu), zinc (Zn), chromium (Cr), manganese (Mn), nickel (Ni), cadmium (Cd), and lead (Pb) in some of the body soaps most commonly used in Bangladesh. The concentrations of Fe, Cu, Zn, Cr, and Mn were found within the acceptable limits stipulated by the World Health Organization (WHO); however, in contrast, the concentrations of Ni, Cd, and Pb remained below the detection limit. Notably, the concentration of Cr in two soap samples (S-2, S-3) out of twenty-one soap samples exceeded the permissible limit stipulated by the WHO. Health risks associated with the TM intake via dermal routes were evaluated in terms of chronic daily intake (CDI) and hazard quotient (HQ). The results indicated that no non-carcinogenic risks (NCR) are likely to occur owing to the use of those body soaps. The carcinogenic risk (CR) estimated for Cr revealed no possibility of probable carcinogenic diseases. Though the NCR and CR are unlikely to occur resulting from the long-term uses of these soaps, the present study provides baseline information on the possible contaminations of TMs in the beauty soaps that do not seem to have been reported so far in Bangladesh. In light of the above information, it can be concluded that the presence of TMs in the body soaps could be a warning for people in general thereby suggesting continuous monitoring.

Prospect of nanomaterials as antimicrobial and antiviral regimen.

In recent years studies of nanomaterials have been explored in the field of microbiology due to the increasing evidence of antibiotic resistance. Nanomaterials could be inorganic or organic, and they may be synthesized from natural products from plant or animal origin. The therapeutic applications of nano-materials are wide, from diagnosis of disease to targeted delivery of drugs. Broad-spectrum antiviral and antimicrobial activities of nanoparticles are also well evident. The ratio of nanoparticles surface area to their volume is high and that allows them to be an advantageous vehicle of drugs in many respects. Effective uses of various materials for the synthesis of nanoparticles impart much specificity in them to meet the requirements of specific therapeutic strategies. The potential therapeutic use of nanoparticles and their mechanisms of action against infections from bacteria, fungi and viruses were the focus of this review. Further, their potential advantages, drawbacks, limitations and side effects are also included here. Researchers are characterizing the exposure pathways of nano-medicines that may cause serious toxicity to the subjects or the environment. Indeed, societal ethical issues in using nano-medicines pose a serious question to scientists beyond anything.

Size controlled biosynthesis of silver nanoparticles using Ophiorrhiza mungos, Ophiorrhiza harrisiana and Ophiorrhiza rugosa aqueous leaf extract and their antimicrobial activity.

In this work, the aqueous leaf extracts of three Ophiorrhiza genus species, namely Ophiorrhiza mungos (Om), Ophiorrhiza harrisiana (Oh) and Ophiorrhiza rugosa (Or), have been used as the reducing and capping agents to control the size of AgNPs, Om-AgNPs, Oh-AgNPs and Or-AgNPs, respectively and found to be an effective antimicrobial agent against a wide range of bacteria and fungi. The biosynthesized AgNPs were studied by UV-Visible spectrophotometer, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray, transmission electron microscopy (TEM) and Fourier transform infrared spectrometer (FTIR). The average particle sizes of Om-AgNPs, Oh-AgNPs and Or-AgNPs were measured as 17 nm, 22 nm and 26 nm, respectively, and observed to be spherical and face-centered cubic crystals. The antibacterial test of synthesized AgNPs was performed against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Vibrio cholerae where the maximum antibacterial activity was observed by reducing the nano-size and increasing the silver content of AgNPs. The antifungal effect of these three types of AgNPs on Penicillium notatum and Aspergillus niger was also evaluated and their growth with AgNPs concentrations of 450 µg/mL was inhibited up to 80-90% and 55-70%, respectively. The size-control synthesis of AgNPs using the Ophiorrhiza genus species is presented here for the first time where the synthesized AgNPs showed higher stability and antimicrobial activities. Therefore, this study might lead to synthesize AgNPs with different morphologies using plant extracts of the same genus but from different species and provide strong encouragement for future applications in treating infectious diseases.

Dual effects of NV-CoV-2 biomimetic polymer: An antiviral regimen against COVID-19.

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19.

Mechanism of Antiviral Activities of Nanoviricide's Platform Technology based Biopolymer (NV-CoV-2).

NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combining NV-CoV-2 therapy with other anti-coronavirus therapies such as Remdesivir (RDV). NV-CoV-2 can encapsulate other antiviral compounds as well. In this study, RDV was encapsulated and protected from serum-mediated degradation in vivo. As a result, RDV was available for a longer period of time to interact with RNA polymerase and inhibit.

Coronavirus management and control: Nutrition and alternative medicines.

Background: In late December 2019, the outbreak of COVID-19 caused by the coronavirus severe acute respiratory syndrome-CoV-2, originated in Wuhan Province, the People's Republic of China (PRC). The rapid and highly infectious virus quickly spread around the country and has become a global pandemic. Thousands of people have been infected, and have died. Scientists around the world are working on the vaccine; however, an effective cure is yet to be developed. Aims: Search to be made on some alternative antiviral components from the rich sources of traditional herbal medicine in India as well as in the PRC. Here we discuss them with references. Methods: The knowledge gained from the literature search of antiviral known herbal products or Ayurvedic medicines that used to be applied against any viral or bacterial infections in the past, may be considered for deployment against COVID-19, and may be rewarded. Results: Many medicinal compounds are extracted from plants and have led to drug discovery. Similarly, plant products and their analogues have been employed as an early line of defense against COVID-19. Conclusion: Research into ethnobotany, phytochemistry, plant physiology and ecology may be important in protecting the global population from current and future pandemics.

Depression and Parkinson's disease: a Chicken-Egg story.

Parkinson's disease (PD) is a neurodegenerative disease, however, besides the motor symptoms, such as rest tremor, hypokinesia, postural instability and rigidity, PD patients have also non-motor symptoms, namely neuropsychiatric disorders. Apart from the required motor symptoms, psychopathological symptoms are very common and include mood disorders, anxiety disorders, hallucinations, psychosis, cognitive deterioration and dementia. The underlying pathophysiological process in PD is mainly due to the loss of dopaminergic neural cells and thereby causes the shortage of nigrostriatal dopamine content in them. In addition, it may involve other neurotransmitter systems such as the noradrenergic, serotonergic, cholinergic and noradrenergic systems as well. Depression can result from any unhealthy conditions making the diagnosis a challenging task. The manifestation of depression associated with or without PD is inadequate. The co-occurrence of depression and PD often leads to the conceptual discussion on whether depressive symptoms appear before or after PD develops. This paper will discuss the conceptual mechanism of PD and depression. Keep in mind both conditions belong to two separate entities but share some similar aspects in their pathophysiology.

Biomarkers and molecular mechanisms of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in adults involving non-demyelinating motor disorders. About 90% of ALS cases are sporadic, while 10-12% of cases are due to some genetic reasons. Mutations in superoxide dismutase 1 (SOD1), TAR, c9orf72 (chromosome 9 open reading frame 72) and VAPB genes are commonly found in ALS patients. Therefore, the mechanism of ALS development involves oxidative stress, endoplasmic reticulum stress, glutamate excitotoxicity and aggregation of proteins, neuro-inflammation and defective RNA function. Cholesterol and LDL/HDL levels are also associated with ALS development. As a result, sterols could be a suitable biomarker for this ailment. The main mechanisms of ALS development are reticulum stress, neuroinflammation and RNA metabolism. The multi-nature development of ALS makes it more challenging to pinpoint a treatment.

A review of possible therapies for Parkinson's disease.

Parkinson's disease (PD) is a complex condition with a wide range of symptoms, like impaired movement, tremors, apathy and depression, and many other symptoms. The disease results from degeneration of dopaminergic neural cells. No cure at present but symptomatic some palliative treatments are available to slow down the disease progression. According to the Parkinson's Foundation every year in U.S., approximately 60,000 Americans diagnosed with PD. Nearly one million will be living with PD in the U.S. by 2020, which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy and Amyotrophic Lateral Sclerosis (ALS). There is no diagnostic test for PD, yet, but this article will review all kinds symptomatic and disease-modifying therapy.

Possible therapies of Parkinson's disease: A review.

Parkinson's disease (PD) is a complex condition with a wide range of symptoms, like impaired movement, tremors, apathy and depression, and many other symptoms. The disease results from degeneration of dopaminergic neural cells. No cure at present but symptomatic some palliative treatments are available to slow down the disease progression. According to the Parkinson's Foundation every year in U.S., approximately 60,000 Americans diagnosed with PD. Nearly one million will be living with PD in the U.S. by 2020, which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy and Amyotrophic Lateral Sclerosis (ALS). There is no diagnostic test for PD, yet, but this article will review all kinds symptomatic and disease-modifying therapy.

Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease.

PURPOSE: Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor). METHODS: Proliferation and apoptosis assays were performed in a large panel of cell lines representing varying receptor expression levels. Mechanistic effects were studied using phospho-protein immunoblotting. Analyses of drug interaction effects were performed using linear mixed-effects regression models. RESULTS: Enhanced anti-proliferative effects of HER/IGF-insulin co-targeting were seen in most, though not all, cell lines, including HER2-normal lines. For ER+ lines, triple targeting with inclusion of anti-estrogen generally resulted in the greatest anti-tumor effects. Double or triple targeting generally resulted in marked increases in apoptosis in the sensitive lines. Mechanistic studies demonstrated that the synergy between drugs was correlated with maximal inhibition of Akt and ERK pathway signaling. CONCLUSIONS: Dual HER/IGF-insulin targeting, and triple targeting with inclusion of anti-estrogen drugs, shows striking anti-tumor activity across breast cancer types, and drugs with broader receptor specificity may be more effective than single receptor selective drugs, particularly for ER- cells.

In vitro and in vivo studies of the combination of IGF1R inhibitor figitumumab (CP-751,871) with HER2 inhibitors trastuzumab and neratinib.

The insulin-like growth factor I receptor (IGF1R) has been linked to resistance to HER2-directed therapy with trastuzumab (Herceptin). We examined the anti-tumor activity of figitumumab (CP-751,871), a human monoclonal antibody that blocks IGF1R ligand binding, alone and in combination with the therapeutic anti-HER2 antibody trastuzumab and the pan-HER family tyrosine kinase inhibitor neratinib, using in vitro and in vivo breast cancer model systems. In vitro assays of proliferation, apoptosis, and signaling, and in vivo anti-tumor experiments were conducted in HER2-overexpressing (BT474) and HER2-normal (MCF7) models. We find single-agent activity of the HER2-targeting drugs but not figitumumab in the BT474 model, while the reverse is true in the MCF7 model. However, in both models, combining figitumumab with HER2-targeting drugs shows synergistic anti-proliferative and apoptosis-inducing effects, and optimum inhibition of downstream signaling. In murine xenograft models, synergistic anti-tumor effects were observed in the HER2-normal MCF7 model for the combination of figitumumab with trastuzumab, and, in the HER2-overexpressing BT474 model, enhanced anti-tumor effects were observed for the combination of figitumumab with either trastuzumab or neratinib. Analysis of tumor extracts from the in vivo experiments showed evidence of the most optimal inhibition of downstream signaling for the drug combinations over the single-agent therapies. These results suggest promise for such combinations in treating patients with breast cancer, and that, unlike the case for single-agent therapy, the therapeutic effects of such combinations may be independent of expression levels of the individual receptors or the single-agent activity profile.

Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or overexpressing breast cancer models.

BACKGROUND: Estrogen receptor (ER) and human epidermal growth factor receptor (HER) family receptors interact in breast cancer; co-targeting these receptors is of interest. We previously reported on a synergistic growth inhibition for the combination of trastuzumab plus tamoxifen in HER2+/ER+ BT474 cells, but no induction of apoptosis. Herein we describe the effects of co-targeting in models of differing HER2 overexpression status (MCF7 HER2-normal/ER+, BT474 HER2-overexpressing/ER+). MATERIALS AND METHODS: Assays of proliferation were carried-out using WST-1, cell cycle using flow cytometry, and apoptosis by determination of sub-G1 population and by annexin-V. RESULTS: Combining a dual HER2/EGFR kinase inhibitor with anti-estrogens induces apoptosis of BT474 cells. Furthermore, in MCF7 cells, despite HER2-normal status and lack of response to single-agent HER2 inhibitors, addition of HER2 inhibitors or dual HER2/EGFR inhibitor to anti-estrogens augments the antiproliferative effect of anti-estrogens, and converts the drug effect from cytostatic to apoptosis-inducing. CONCLUSION: ER-HER co-targeting enhanced the antitumor effects and can bring about effects of targeting HER2 in models of HER2-normal breast cancer.

Fabrication of Bi2O3/TiO2 nanocomposites and their applications to the degradation of pollutants in air and water under visible-light.

A nanoheterojunction composite photocatalyst Bi2O3/TiO2 working under visible-light (lambda > or = 420 nm) was prepared by combining two semiconductors Bi2O3 and TiO2 varying the Bi2O3/TiO2 molar ratio. Maleic acid was employed as an organic binder to unite Bi2O3 and TiO2 nanoparticles. The SEM, TEM, XRD and diffuse reflectance spectra were utilized to characterize the prepared Bi2O3/TiO2 nanoheterojunction. The nanocomposite exhibited unusual high photocatalytic activity in decomposing 2-propanol in gas phase and phenol in aqueous phase and, evolution of CO2 under visible light irradiation while the end members exhibited low photocatalytic activity. The composite was optimized to 5 mol% Bi2O3/TiO2. The remarkable high photocatalytic efficiency originates from the unique relative energy band position of Bi2O3 and TiO2 as well as the absorption of visible light by Bi2O3.

Genotype-selective combination therapies for melanoma identified by high-throughput drug screening.

UNLABELLED: Resistance and partial responses to targeted monotherapy are major obstacles in cancer treatment. Systematic approaches to identify efficacious drug combinations for cancer are not well established, especially in the context of genotype. To address this, we have tested pairwise combinations of an array of small-molecule inhibitors on early-passage melanoma cultures using combinatorial drug screening. Results reveal several inhibitor combinations effective for melanomas with activating RAS or BRAF mutations, including mutant BRAF melanomas with intrinsic or acquired resistance to vemurafenib. Inhibition of both EGF receptor and AKT sensitized treatment-resistant BRAF mutant melanoma cultures to vemurafenib. Melanomas with RAS mutations were more resistant to combination therapies relative to BRAF mutants, but were sensitive to combinations of statins and cyclin-dependent kinase inhibitors in vitro and in vivo. These results show the use of combinatorial drug screening for discovering unique treatment regimens that overcome resistance phenotypes of mutant BRAF- and RAS-driven melanomas. SIGNIFICANCE: We have used drug combinatorial screening to identify effective combinations for mutant BRAF melanomas, including those resistant to vemurafenib, and mutant RAS melanomas that are resistant to many therapies. Mechanisms governing the interactions of the drug combinations are proposed, and in vivo xenografts show the enhanced benefit and tolerability of a mutant RAS -selective combination, which is currently lacking in the clinic.

Leukocyte-cancer cell fusion: initiator of the warburg effect in malignancy?

The causes of metastasis remain unknown, however it has been proposed for nearly a century that metastatic cells are generated by fusion of tumor cells with tumor-associated leukocytes such as macrophages. Indeed, regardless of cell or tissue origin, when cancer cells in the original in situ tumor transform to malignant, invasive cells, they generally become aneuploid and begin to express molecules and traits characteristic of activated macrophages. This includes two key features of malignancy: chemotactic motility and the use of aerobic glycolysis as a metabolic energy source (the Warburg effect). Here we review evidence that these phenomena can be well-explained by macrophage-cancer cell fusion, as evidenced by studies of experimental macrophage-melanoma hybrids generated in vitro and spontaneous host-tumor hybrids in animals and more recently humans. A key finding to emerge is that experimental and spontaneous cancer cell hybrids alike displayed a high degree of constitutive autophagy, a macrophage trait that is expressed under hypoxia and nutrient deprivation as part of the Warburg effect. Subsequent surveys of 21 different human cancers from nearly 2,000 cases recently revealed that the vast majority (~85%) exhibited autophagy and that this was associated with tumor proliferation and metastasis. While much work needs to be done, we posit that these findings with human cancers could be a reflection of widespread leukocyte-cancer cell fusion as an initiator of metastasis. Such fusions would generate hybrids that express the macrophage capabilities for motility and survival under adverse conditions of hypoxia and nutrient deprivation, while at the same time maintaining the deregulated mitotic cycle of the cancer cell fusion partner.

Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines.

The insulin-like growth factor I receptor (IGF1R) interacts with estrogen receptor-alpha (ERalpha) and HER2. We examined the effect of combinations of IGF1R antagonists (alpha-IR3, AG1024) and anti-estrogens (4-hydroxy tamoxifen, fulvestrant) in two human ER+ breast cancer cell lines: BT474 (HER2 overexpressing, IGF1R low) and MCF7 (HER2 non-overexpressing, IGF1R high). In BT474 cells, growth was inhibited by anti-estrogens, but not by IGF1R antagonists; however, adding IGF1R inhibitors to anti-estrogens enhanced growth inhibition. In MCF7 cells, growth was inhibited by IGF1R and ER antagonists and more so by their combination. In both cell lines, no single agents could induce apoptosis, but combining IGF1R inhibitors with anti-estrogens induced dramatic levels of apoptosis. IGF1R antagonists enhanced the ability of the anti-estrogens to inhibit ER transcriptional activity in BT474 cells, but not in MCF7 cells. The drug combination synergistically inhibited ER and IGF1R activity. Such combinations may be useful therapy for breast cancer.

Upregulation of alpha and beta integrin subunits in metastatic macrophage-melanoma fusion hybrids.

Fusion of cancer cells with migratory bone-marrow-derived cells such as macrophages can produce cancer cells with increased metastatic potential. To study this, we fused mouse macrophages with weakly metastatic mouse melanoma cells and generated a panel of hybrid clones. About half of these showed increased metastatic potential in mice. These hybrids expressed traits and molecules that were known indicators of tumor progression in melanoma (chemotaxis toward fibronectin, melanogenesis, autophagy, cMet, MCR1, SPARC, cell surface LAMP-1, GnT-V and ß1,6-branched oligosaccharides). Here, we investigated integrin subunit expression in selected hybrids. Integrins, especially those that are substrates for the glycosyltransferase GnT-V and carriers of ß1,6-branched oligosaccharides, play an important role in cell migration. We report increased expression of the integrin subunits α3, α5, α6, αv, ß1, and ß3 in metastatic hybrids compared with parental melanoma cells and a weakly metastatic hybrid. Notably, each of these subunits is also a substrate for GnT-V. Integrin subunit expression was further increased by inducers of cyclic AMP. Expression of these integrin subunits is a characteristic of macrophages and also associated with progression in melanoma and other cancers. In summary, our studies of macrophage-melanoma hybrids show that several α and ß integrin subunits are upregulated in the metastatic lines. This adds further support for the theory that generation of a metastatic phenotype may be initiated through a single event: fusion of migratory bone marrow-derived cells with cancer cells.