Live bacteria were first actively used in the treatment of cancer nearly 150 years ago, work that... more Live bacteria were first actively used in the treatment of cancer nearly 150 years ago, work that ultimately led to the study of immunomodulation. Today, with the discovery of bacterial strains that specifically target tumours, and aided by genomic sequencing and genetic engineering, there is new interest in the use of bacteria as tumour vectors. Bifodobacterium, Clostridium, and Salmonella have all been shown to preferentially replicate within solid tumours when injected from a distal site, and all three types of bacteria have been used to transport and amplify genes encoding factors such as prodrug-converting enzymes, toxins, angiogenesis inhibitors, and cytokines. In this review we provide a historical discussion of this area, and describe the development of the bacteria, which are currently being prepared for use in clinical trials in patients with cancer.
We examine the hypothesis that, in the origin of species and higher taxa of eukaryotes, symbiont ... more We examine the hypothesis that, in the origin of species and higher taxa of eukaryotes, symbiont acquisition followed by partner integration has been equivalent to neoseme appearance leading to speciation. The formation of stable symbiotic associations involves partner-surface recognition, behavioral and metabolic interaction, and, in some cases, gene product (RNA, protein) and genic (RNA, DNA) integration. This analysis is applied here to examples of neosemes that define specific taxa and to neosemes in plants, fungi, and animals that involve the appearance of new types of tissue. If this hypothesis is correct--if the origin of major genetic variation leading to speciation and even higher taxa may occur through symbiont acquisition and integration--then the analysis of "origins of species and higher taxa" becomes analogous to the study of microbial community ecology.
Lipid A, a potent endotoxin which can cause septic shock, anchors lipopolysaccharide (LPS) into t... more Lipid A, a potent endotoxin which can cause septic shock, anchors lipopolysaccharide (LPS) into the outer leaflet of the outer membrane of gram-negative bacteria. MsbB acylates (KDO) 2 -(lauroyl)-lipid IV-A with myristate during lipid A biosynthesis. Reports of knockouts of the msbB gene describe effects on virulence but describe no evidence of growth defects in Escherichia coli K-12 or Salmonella . Our data confirm the general lack of growth defects in msbB E. coli K-12. In contrast, msbB Salmonella enterica serovar Typhimurium exhibits marked sensitivity to galactose-MacConkey and 6 mM EGTA media. At 37°C in Luria-Bertani (LB) broth, msbB Salmonella cells elongate, form bulges, and grow slowly. msbB Salmonella grow well on LB-no salt (LB-0) agar; however, under specific shaking conditions in LB-0 broth, many msbB Salmonella cells lyse during exponential growth and a fraction of the cells form filaments. msbB Salmonella grow with a near-wild-type growth rate in MSB (LB-0 containing...
Brocchinia reducta, a tank-forming member of subfamily Pitcairnioideae (Bromeliaceae), possesses ... more Brocchinia reducta, a tank-forming member of subfamily Pitcairnioideae (Bromeliaceae), possesses foliar trichomes capable of absorbing 3H-leucine as do those borne by other members of the same family (all Tillandsioideae and some species of Bromelioideae). In general, pitcairnioid trichomes have been considered incapable of participating in nutrient uptake. Other features of leaf anatomy and physiology, such as the presence of the C3 photosynthetic pathway, suggest that either 1) Brocchinia and tillandsioid tank shoots bearing absorptive hairs are a result of convergence or 2) both subfamilies acquired this feature from the same ancestor. All in all, Tillandsioideae and Pitcairnioideae share more vegetative features in common than either does with Bromelioideae and, thus, may be more closely related than was previously suspected. Tank deployment in Bromelioideae seems to have originated independently from a semi-xeric terrestrial habit that incorporated the CAM syndrome. Factors that could have led to the emergence of absorptive trichomes in Bromeliaceae are identified.
Manuscript Files Type Fig/Table # Filename Size Uploaded manuscript Quintero and Bermudes 2014, J... more Manuscript Files Type Fig/Table # Filename Size Uploaded manuscript Quintero and Bermudes 2014, J Microbiol Methods 1-s2.0-S0167701214000591main.pdf 511809 2014-03-15 19:44:16 This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2-3 weeks time). Any corrections that need to be made will be done at that time. No materials will be released to PMC without the approval of an author.
Studies were conducted on the hypothesis that melanoma metastasis might be initiated through the ... more Studies were conducted on the hypothesis that melanoma metastasis might be initiated through the generation of hybrids comprised of cells of the primary tumor and tumor-infiltrating leukocytes. Fusion hybrids were generated in vitro between weakly metastatic Cloudman S91 mouse melanoma cells and normal mouse or human macrophages. Hybrids were implanted s.c. in the tail and mice were monitored for metastases. Controls included parental S91 cells, autologous S91 x S91 hybrids, and B16F10 melanoma cells. Of 35 hybrids tested, most were more aggressive than the parental melanoma cells, producing metastases sooner and in more mice. A striking characteristic was heterogeneity amongst hybrids, with some lines producing no metastases and others producing metastases in up to 80% of mice. With few exceptions, hybrids with the highest metastatic potential also had the highest basal melanin content whereas those with the lowest metastatic potential were basally amelanotic, as were the parental ...
The microbial communities in two sites were studied using several approaches: (1) light microscop... more The microbial communities in two sites were studied using several approaches: (1) light microscopy; (2) the measurement of microprofiles of oxygen and sulfide at the surface of the microbial mat; (3) the study of diurnal variation of oxygen and sulfides; (4) in situ measurement of photosynthesis and sulfate reduction and study of the coupling of these two processes; (5) measurement of glutathione in the upper layers of the microbial mat as a possible oxygen quencher; (6) measurement of reduced iron as a possible intermediate electron donor along the established redoxcline in the mats; (7) measurement of dissolved phosphate as an indicator of processes of break down of organic matter in these systems; and (8) measurement of carbon dioxide in the interstitial water and its delta C-13 in an attempt to understand the flow of CO2 through the systems. Microbial processes of primary production and initial degradation at the most active zone of the microbial mat were analyzed.
We present a phenomenological method for predicting the number of Flat Spectrum Radio Quasars (FS... more We present a phenomenological method for predicting the number of Flat Spectrum Radio Quasars (FSRQs) that should be detected by upcoming Square Kilometer Array (SKA) SKA1-MID Wide Band 1 and Medium-Deep band 2 surveys. We use the Fermi Blazar Sequence and mass estimates of Fermi FSRQs, and γ-ray emitting Narrow Line Seyfert 1 galaxies, to model the radio emission of FSRQs as a function of mass alone, assuming a near-Eddington accretion rate, which is suggested by current quasar surveys at z 6. This is used to determine the smallest visible black hole mass as a function of redshift in two competing cosmologies we compare in this paper: the standard ΛCDM model and the R h = ct universe. We then apply lockstep growth to the observed black-hole mass function at z = 6 in order to devolve that population to higher redshifts and determine the number of FSRQs detectable by the SKA surveys as a function of z. We find that at the redshifts for which this method is most valid, ΛCDM predicts ∼ 30 times more FSRQs than R h = ct for the Wide survey, and ∼ 100 times more in the Medium-Deep survey. These stark differences will allow the SKA surveys to strongly differentiate between these two models, possibly rejecting one in comparison with the other at a high level of confidence.
Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, al... more Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, although its use could be limited by the potential induction of tumor necrosis factor alpha (TNFalpha)-mediated septic shock stimulated by lipid A. Genetic modifications of tumor-targeting Salmonella that alter lipid A and increase safety must, however, retain the useful properties of this bacteria. We report here that disruption of the Salmonella msbB gene reduces TNFalpha induction and increases the LD50 of this pathogenic bacteria by 10,000-fold. Notwithstanding this enormous difference, Salmonella retains its tumor-targeting properties, exhibiting tumor accumulation ratios in excess of 1000:1 compared with normal tissues. Administration of this bacteria to mice bearing melanoma results in tumors that are less than 6% the size of tumors in untreated controls at day 18. Thus, the antitumor activity previously demonstrated using tumor-targeting Salmonella with normal lipid A is retained. Lipid modification of tumor-specific bacterial vectors provides a means for reducing septic shock and further suggests that the antitumor activity of these bacteria may be independent of TNFalpha.
Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate protozoan paras... more Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate protozoan parasite Toxoplasma gondii. The protein has apyrase activity, degrading ATP to the di- and mono-phosphate forms. Because T. gondii is incapable of de novo synthesis of purines, it is postulated that NTPase may be used by the parasite to salvage purines from the host cell for survival and replication. To elucidate the molecular mechanisms of NTP gene expression, we isolated from the virulent RH strain of T. gondii the putative promoter region of three tandemly repeated NTP genes (NTP1, 2, 3). Using deletion constructs linked to the chloramphenicol acetyl transferase (CAT) reporter gene, we defined an active promoter within the first 220 bp. Sequence analysis of this region reveals the lack of a TATA box, but the promoter region is associated with a sequence which resembles an initiator element (Inr) in the NTP1 and NTP3 genes. This sequence which is similar to other Inrs known to regulate the expression of a wide variety of RNA polymerase II genes, is required for NTP expression. The NTP3 promoter contains sufficient information for developmentally regulated expression of CAT activity when the actively replicating stage tachyzoite differentiates into the dormant bradyzoite form.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 2001
ALLenuaLed strains of Salmonella typhimurium, VNP20009 aml YS7212, when injected sy>temically to ... more ALLenuaLed strains of Salmonella typhimurium, VNP20009 aml YS7212, when injected sy>temically to tumor-bearing mice, accumulated prctcrentially in tumors at levels at least 200-fold and, more commonly, I 000-fold greater than in other normal tissues. This selectivity occurred in subcutaneously implanted murine tumors, includin g B l6FIO melanoma, :v127 lung carcinorn<t, and colon 38 carcinoma. The preferential accumulation was also manifested in animals bearing human tumor xenografts, including Lox, C81 86, DLDl. SW620, HCTl l6. HTB 177, DU145. MDA-MB-231, and Caki. Four to five days afler a single IV injection of l x lO' rolony-forming unit (cfu)/mouse, we routinely detected VNP20009 prolifer ation and accumulation at levels ranging from l x 10" to 2 x to'' cfu/g tumor. The amount of VNP20009 accumulated in the liver ranged from 3 x 10 ' to 2 x 10 " cfu/g. The distribution of Salmonella in tumors was homogenous; YS72l2 cnuld he detected from the periphery to the interior portion of the tumors_ Usmg mice wit h various immunodeficiencies. we also discuvert:d the same preferential accumulation of Salmonella in tumors implanted in these mice_ The use of S<Ilmonel/o as a protein delivery vector was shown by IV administration of the bacteria expressing either green t1uorescent protein (GFP) or cytosine deaminase (CD) into tumor-bearing mice. GFP and CD were detected in tumors, but nul in livers, taken from mice inoculated with Salmonella carrying these gen es. Bacteria accumulation and CD expression persisted in the tumor.s tor up to 14 days after a single bolus IV administration of hacteria to tumor-bearing mice.
Several theories for the origin of eukaryotic (nucleated) cells from prokaryotic (bacterial) ance... more Several theories for the origin of eukaryotic (nucleated) cells from prokaryotic (bacterial) ancestors have been published: the progenote, the direct filiation and the serial endosymbiotic theory (SET). Compelling evidence for two aspects of the SET is now available suggesting that both mitochondria and plastids originated by symbioses with a third type of microbe, probably a Thermoplasma-like archaebacterium ancestral to the nucleocytoplasm. We conclude that not enough information is available to negate or substantiate another SET hypothesis: that the undulipodia (cilia, eukaryotic flagella) evolved from spirochetes. Recognizing the power of symbiosis to recombine in single individual semes from widely differing partners, we develop the idea that symbiosis has been important in the origin of species and higher taxa. The abrupt origin of novel life forms through the formation of stable symbioses is consistent with certain patterns of evolution (e.g punctuated equilibria) described b...
Advances in experimental medicine and biology, 2000
Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tu... more Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tumors, including melanoma, lung, colon, breast, kidney and liver. These bacteria target tumors after systemic administration and selectively replicate within them. Specificity for tumors is often more than 1,000 times greater than for any other tissue. Auxotrophic mutations make these bacteria highly safe and form the basis for maintaining tumor specificity. An altered lipid greatly reduces the potential for septic shock yet also retains the antitumor properties of these bacteria. These bacteria have innate antitumor activity towards both primary and metastatic tumors and the ability to deliver proteins capable of activating chemotherapeutic agents directly within tumors. The delay in tumor growth results in mice that survive up to twice as long. These bacteria are susceptible to a wide range of antibiotics, allowing external control of the vector after administration. The combination of ...
Live bacteria were first actively used in the treatment of cancer nearly 150 years ago, work that... more Live bacteria were first actively used in the treatment of cancer nearly 150 years ago, work that ultimately led to the study of immunomodulation. Today, with the discovery of bacterial strains that specifically target tumours, and aided by genomic sequencing and genetic engineering, there is new interest in the use of bacteria as tumour vectors. Bifodobacterium, Clostridium, and Salmonella have all been shown to preferentially replicate within solid tumours when injected from a distal site, and all three types of bacteria have been used to transport and amplify genes encoding factors such as prodrug-converting enzymes, toxins, angiogenesis inhibitors, and cytokines. In this review we provide a historical discussion of this area, and describe the development of the bacteria, which are currently being prepared for use in clinical trials in patients with cancer.
We examine the hypothesis that, in the origin of species and higher taxa of eukaryotes, symbiont ... more We examine the hypothesis that, in the origin of species and higher taxa of eukaryotes, symbiont acquisition followed by partner integration has been equivalent to neoseme appearance leading to speciation. The formation of stable symbiotic associations involves partner-surface recognition, behavioral and metabolic interaction, and, in some cases, gene product (RNA, protein) and genic (RNA, DNA) integration. This analysis is applied here to examples of neosemes that define specific taxa and to neosemes in plants, fungi, and animals that involve the appearance of new types of tissue. If this hypothesis is correct--if the origin of major genetic variation leading to speciation and even higher taxa may occur through symbiont acquisition and integration--then the analysis of "origins of species and higher taxa" becomes analogous to the study of microbial community ecology.
Lipid A, a potent endotoxin which can cause septic shock, anchors lipopolysaccharide (LPS) into t... more Lipid A, a potent endotoxin which can cause septic shock, anchors lipopolysaccharide (LPS) into the outer leaflet of the outer membrane of gram-negative bacteria. MsbB acylates (KDO) 2 -(lauroyl)-lipid IV-A with myristate during lipid A biosynthesis. Reports of knockouts of the msbB gene describe effects on virulence but describe no evidence of growth defects in Escherichia coli K-12 or Salmonella . Our data confirm the general lack of growth defects in msbB E. coli K-12. In contrast, msbB Salmonella enterica serovar Typhimurium exhibits marked sensitivity to galactose-MacConkey and 6 mM EGTA media. At 37°C in Luria-Bertani (LB) broth, msbB Salmonella cells elongate, form bulges, and grow slowly. msbB Salmonella grow well on LB-no salt (LB-0) agar; however, under specific shaking conditions in LB-0 broth, many msbB Salmonella cells lyse during exponential growth and a fraction of the cells form filaments. msbB Salmonella grow with a near-wild-type growth rate in MSB (LB-0 containing...
Brocchinia reducta, a tank-forming member of subfamily Pitcairnioideae (Bromeliaceae), possesses ... more Brocchinia reducta, a tank-forming member of subfamily Pitcairnioideae (Bromeliaceae), possesses foliar trichomes capable of absorbing 3H-leucine as do those borne by other members of the same family (all Tillandsioideae and some species of Bromelioideae). In general, pitcairnioid trichomes have been considered incapable of participating in nutrient uptake. Other features of leaf anatomy and physiology, such as the presence of the C3 photosynthetic pathway, suggest that either 1) Brocchinia and tillandsioid tank shoots bearing absorptive hairs are a result of convergence or 2) both subfamilies acquired this feature from the same ancestor. All in all, Tillandsioideae and Pitcairnioideae share more vegetative features in common than either does with Bromelioideae and, thus, may be more closely related than was previously suspected. Tank deployment in Bromelioideae seems to have originated independently from a semi-xeric terrestrial habit that incorporated the CAM syndrome. Factors that could have led to the emergence of absorptive trichomes in Bromeliaceae are identified.
Manuscript Files Type Fig/Table # Filename Size Uploaded manuscript Quintero and Bermudes 2014, J... more Manuscript Files Type Fig/Table # Filename Size Uploaded manuscript Quintero and Bermudes 2014, J Microbiol Methods 1-s2.0-S0167701214000591main.pdf 511809 2014-03-15 19:44:16 This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2-3 weeks time). Any corrections that need to be made will be done at that time. No materials will be released to PMC without the approval of an author.
Studies were conducted on the hypothesis that melanoma metastasis might be initiated through the ... more Studies were conducted on the hypothesis that melanoma metastasis might be initiated through the generation of hybrids comprised of cells of the primary tumor and tumor-infiltrating leukocytes. Fusion hybrids were generated in vitro between weakly metastatic Cloudman S91 mouse melanoma cells and normal mouse or human macrophages. Hybrids were implanted s.c. in the tail and mice were monitored for metastases. Controls included parental S91 cells, autologous S91 x S91 hybrids, and B16F10 melanoma cells. Of 35 hybrids tested, most were more aggressive than the parental melanoma cells, producing metastases sooner and in more mice. A striking characteristic was heterogeneity amongst hybrids, with some lines producing no metastases and others producing metastases in up to 80% of mice. With few exceptions, hybrids with the highest metastatic potential also had the highest basal melanin content whereas those with the lowest metastatic potential were basally amelanotic, as were the parental ...
The microbial communities in two sites were studied using several approaches: (1) light microscop... more The microbial communities in two sites were studied using several approaches: (1) light microscopy; (2) the measurement of microprofiles of oxygen and sulfide at the surface of the microbial mat; (3) the study of diurnal variation of oxygen and sulfides; (4) in situ measurement of photosynthesis and sulfate reduction and study of the coupling of these two processes; (5) measurement of glutathione in the upper layers of the microbial mat as a possible oxygen quencher; (6) measurement of reduced iron as a possible intermediate electron donor along the established redoxcline in the mats; (7) measurement of dissolved phosphate as an indicator of processes of break down of organic matter in these systems; and (8) measurement of carbon dioxide in the interstitial water and its delta C-13 in an attempt to understand the flow of CO2 through the systems. Microbial processes of primary production and initial degradation at the most active zone of the microbial mat were analyzed.
We present a phenomenological method for predicting the number of Flat Spectrum Radio Quasars (FS... more We present a phenomenological method for predicting the number of Flat Spectrum Radio Quasars (FSRQs) that should be detected by upcoming Square Kilometer Array (SKA) SKA1-MID Wide Band 1 and Medium-Deep band 2 surveys. We use the Fermi Blazar Sequence and mass estimates of Fermi FSRQs, and γ-ray emitting Narrow Line Seyfert 1 galaxies, to model the radio emission of FSRQs as a function of mass alone, assuming a near-Eddington accretion rate, which is suggested by current quasar surveys at z 6. This is used to determine the smallest visible black hole mass as a function of redshift in two competing cosmologies we compare in this paper: the standard ΛCDM model and the R h = ct universe. We then apply lockstep growth to the observed black-hole mass function at z = 6 in order to devolve that population to higher redshifts and determine the number of FSRQs detectable by the SKA surveys as a function of z. We find that at the redshifts for which this method is most valid, ΛCDM predicts ∼ 30 times more FSRQs than R h = ct for the Wide survey, and ∼ 100 times more in the Medium-Deep survey. These stark differences will allow the SKA surveys to strongly differentiate between these two models, possibly rejecting one in comparison with the other at a high level of confidence.
Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, al... more Systemically administered tumor-targeted Salmonella has been developed as an anticancer agent, although its use could be limited by the potential induction of tumor necrosis factor alpha (TNFalpha)-mediated septic shock stimulated by lipid A. Genetic modifications of tumor-targeting Salmonella that alter lipid A and increase safety must, however, retain the useful properties of this bacteria. We report here that disruption of the Salmonella msbB gene reduces TNFalpha induction and increases the LD50 of this pathogenic bacteria by 10,000-fold. Notwithstanding this enormous difference, Salmonella retains its tumor-targeting properties, exhibiting tumor accumulation ratios in excess of 1000:1 compared with normal tissues. Administration of this bacteria to mice bearing melanoma results in tumors that are less than 6% the size of tumors in untreated controls at day 18. Thus, the antitumor activity previously demonstrated using tumor-targeting Salmonella with normal lipid A is retained. Lipid modification of tumor-specific bacterial vectors provides a means for reducing septic shock and further suggests that the antitumor activity of these bacteria may be independent of TNFalpha.
Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate protozoan paras... more Nucleoside triphosphate hydrolase is an abundant protein secreted by the obligate protozoan parasite Toxoplasma gondii. The protein has apyrase activity, degrading ATP to the di- and mono-phosphate forms. Because T. gondii is incapable of de novo synthesis of purines, it is postulated that NTPase may be used by the parasite to salvage purines from the host cell for survival and replication. To elucidate the molecular mechanisms of NTP gene expression, we isolated from the virulent RH strain of T. gondii the putative promoter region of three tandemly repeated NTP genes (NTP1, 2, 3). Using deletion constructs linked to the chloramphenicol acetyl transferase (CAT) reporter gene, we defined an active promoter within the first 220 bp. Sequence analysis of this region reveals the lack of a TATA box, but the promoter region is associated with a sequence which resembles an initiator element (Inr) in the NTP1 and NTP3 genes. This sequence which is similar to other Inrs known to regulate the expression of a wide variety of RNA polymerase II genes, is required for NTP expression. The NTP3 promoter contains sufficient information for developmentally regulated expression of CAT activity when the actively replicating stage tachyzoite differentiates into the dormant bradyzoite form.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 2001
ALLenuaLed strains of Salmonella typhimurium, VNP20009 aml YS7212, when injected sy>temically to ... more ALLenuaLed strains of Salmonella typhimurium, VNP20009 aml YS7212, when injected sy>temically to tumor-bearing mice, accumulated prctcrentially in tumors at levels at least 200-fold and, more commonly, I 000-fold greater than in other normal tissues. This selectivity occurred in subcutaneously implanted murine tumors, includin g B l6FIO melanoma, :v127 lung carcinorn<t, and colon 38 carcinoma. The preferential accumulation was also manifested in animals bearing human tumor xenografts, including Lox, C81 86, DLDl. SW620, HCTl l6. HTB 177, DU145. MDA-MB-231, and Caki. Four to five days afler a single IV injection of l x lO' rolony-forming unit (cfu)/mouse, we routinely detected VNP20009 prolifer ation and accumulation at levels ranging from l x 10" to 2 x to'' cfu/g tumor. The amount of VNP20009 accumulated in the liver ranged from 3 x 10 ' to 2 x 10 " cfu/g. The distribution of Salmonella in tumors was homogenous; YS72l2 cnuld he detected from the periphery to the interior portion of the tumors_ Usmg mice wit h various immunodeficiencies. we also discuvert:d the same preferential accumulation of Salmonella in tumors implanted in these mice_ The use of S<Ilmonel/o as a protein delivery vector was shown by IV administration of the bacteria expressing either green t1uorescent protein (GFP) or cytosine deaminase (CD) into tumor-bearing mice. GFP and CD were detected in tumors, but nul in livers, taken from mice inoculated with Salmonella carrying these gen es. Bacteria accumulation and CD expression persisted in the tumor.s tor up to 14 days after a single bolus IV administration of hacteria to tumor-bearing mice.
Several theories for the origin of eukaryotic (nucleated) cells from prokaryotic (bacterial) ance... more Several theories for the origin of eukaryotic (nucleated) cells from prokaryotic (bacterial) ancestors have been published: the progenote, the direct filiation and the serial endosymbiotic theory (SET). Compelling evidence for two aspects of the SET is now available suggesting that both mitochondria and plastids originated by symbioses with a third type of microbe, probably a Thermoplasma-like archaebacterium ancestral to the nucleocytoplasm. We conclude that not enough information is available to negate or substantiate another SET hypothesis: that the undulipodia (cilia, eukaryotic flagella) evolved from spirochetes. Recognizing the power of symbiosis to recombine in single individual semes from widely differing partners, we develop the idea that symbiosis has been important in the origin of species and higher taxa. The abrupt origin of novel life forms through the formation of stable symbioses is consistent with certain patterns of evolution (e.g punctuated equilibria) described b...
Advances in experimental medicine and biology, 2000
Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tu... more Genetically engineered Salmonella offer an intriguing new approach to selectively target solid tumors, including melanoma, lung, colon, breast, kidney and liver. These bacteria target tumors after systemic administration and selectively replicate within them. Specificity for tumors is often more than 1,000 times greater than for any other tissue. Auxotrophic mutations make these bacteria highly safe and form the basis for maintaining tumor specificity. An altered lipid greatly reduces the potential for septic shock yet also retains the antitumor properties of these bacteria. These bacteria have innate antitumor activity towards both primary and metastatic tumors and the ability to deliver proteins capable of activating chemotherapeutic agents directly within tumors. The delay in tumor growth results in mice that survive up to twice as long. These bacteria are susceptible to a wide range of antibiotics, allowing external control of the vector after administration. The combination of ...
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