Biology subjects

Lusi, E. A.

Publications and source records attributed to Lusi, E. A..

4 recordsLinked to original sources

bioRxiv2026

A Living Oncogenic Microcell Isolated from Mammalian Cancers

The biological mechanisms underlying oncogenesis are traditionally interpreted within the frameworks of somatic mutation, clonal evolution, and, in some cases, viral infection. Here, we report the isolation, purification and characterization of a distinct class of autonomous microcellular organisms consistently recovered from independent mammalian neoplastic tissues. These entities measure approximately 1-3 microns in diameter and exhibit a reproducible organic wall assembly with internal compartmentalization revealed by transmission and scanning electron microscopy. Biochemical and molecular analyses demonstrated a predominantly RNA-based genetic system associated with intrinsic reverse transcriptase activity. High-throughput sequencing revealed a highly distributed multipartite genetic repertoire comprising approximately 2.63 Mb organized across 1,597 independent RNA units. Canonical bacterial signatures, including 16S ribosomal RNA, were not detected, and the recovered architecture lacked the genomic organization characteristic of known retroviruses. Instead, multiple RNA units contained domains related to reverse transcriptase, mobile genetic elements, regulatory functions, and oncogene-associated sequences. Purified preparations containing intact microcells induced rapid cellular transformation in vitro and aggressive malignancies in murine models. In contrast, matched preparations filtered through a 0.2 micron membrane failed to exhibit reverse transcriptase activity, cellular transformation, or tumorigenicity, demonstrating that the observed biological effects reside within intact micron-scale particles rather than filterable viral agents or soluble components. Furthermore, vaccination targeting the microcellular organisms was associated with tumour regression and restoration of tissue architecture in dogs with naturally occurring cancers. Collectively, these findings describe a previously unrecognized autonomous microcell lineage within mammalian hosts possessing distinctive structural, genetic and biological properties. The combination of cellular organization, a highly distributed multipartite RNA repertoire, intrinsic reverse transcriptase activity, and oncogenic potential suggest a biological strategy not readily accommodated within current frameworks of cancer biology, virology or cellular evolution.

cancer biology↗

bioRxiv2020

A transforming giant virus discovered in Canine Transmissible Venereal Tumour: Stray dogs and Tasmanian devils opening the door to a preventive cancer vaccine.

BackgroundCanine Transmissible Venereal Tumour (CTVT) along with Tasmanian Devil Facial Tumour and transmissible leukaemia in Mya Arenaria soft shell-clams are the only examples of contagious cancers occurring in nature. In particular, CTVT is the oldest contagious cancer present in the wild world. The attempts to detect a transmissible virus as a causative agent in these forms of contagious cancer proved conflicting and the current consensus view is that a transformed somatic cell itself is transmitted and starts the tumor in a new animal, as a parasitic allograft. We modify this perception and report for the first time the isolation of an acutely transforming agent from CTVT. MethodsLarge particles were successfully isolated from CTVT specimens through a sucrose gradient, examined at electron microscopy, fully sequenced, used for transformation tests on NIH-3T3 cells and tumorigenic experiments in dogs. A neutralizing therapeutic vaccine was also administered in dogs with natural, not-induced CTVT. ResultsThe particles, isolated from CTVT, are infectious living entities with large dimension. Electron Microscopy reconstructed an organic wall assemblage pattern typical of early life fossils from the Precambrian age, time at which Earth began to form 4.6 billion years ago. Astonishingly, our agents are not fossils, but unicellular organisms biologically active and acutely transforming. They transformed NIH-3T3 cells in vitro and initiated the typical CTVT lesions in healthy dogs, just one week post-infection. Only the fraction containing these infectious entities were able to induce cancer, while a filtered supernatant did not. This ruled out the presence of conventional filterable viruses. RNA sequencing and bioinformatics analyses disclosed a large genome composed by an almost complete Orphan genes dataset, with retro-elements distinct from the host genome. Five doses of a neutralizing vaccine against these oncogenic organisms, drastically reduced the neoplastic mass in dogs with natural, not-induced CTVT. Analogous infectious agents, acutely transforming were also isolated from several human neoplasms. ConclusionsModifying the current believe that contagious cancers are transmitted by a somatic cells allograft, we identified a living agent that infects and starts the typical CTVT in healthy dogs, while its neutralization with a vaccine induces cancer regression in animals with cancer. Significance StatementThese infectious living single-cell agents establish a new family of oncogenic organisms that resist current classifications and affect humans and animals in the wild. While only a dozen of proteins compose a classic virus, these organisms are small infectious cells, but very distinct from somatic eukaryotic cells. The identification of causative unicellular organisms that start cancer in healthy subjects and the possibility to induce cancer regression with a neutralizing vaccine change some perspectives in cancer. The Precambrian features and the genetic composition suggest that these unicellular entities are infectious living RNA protocells that finally gives form to what was considered only a hypothesis drafted by the Nobel laureate Walter Gilmore: the RNA world, the origin of life and RNA protocells.

cancer biology↗

bioRxiv2019

Discovery Of The First Human Retro-Giant Virus: Description of its morphology, retroviral kinase and ability to induce tumours in mice

BackgroundThe study of retroviruses dates back to the early 1900s during investigations on neoplastic diseases in chickens. Subsequently, Robert Gallo reported the first human retrovirus HLTV in 1980. What we report here is not an archetypal retrovirus, but the discovery of an oncogenic giant microbial agent with a mega-genome, where the transforming retroviral nature co-exists with multiple archaeal oncogenes. MethodsAfter their isolation from human T cells Leukaemia, these organisms were examined at electron microscopy, tested for reverse transcriptase activity, fully sequenced, used for transformation tests on NIH-3T3 cells in vitro and tumours formation in mice. Same type of particles were also isolated from Canine Transmissible Venereal Tumour (CTVT), the oldest contagious cancer in nature. ResultsEM showed the presence of giant viral particles displaying retroviral antigens. These microbial entities harbour in their mega-genome a transforming retroviral kinase, cell-based oncogenes and have reverse transcriptase activity. The purified viral particles transformed NIH-3T3 cells and induced metastatic tumours in nude mice, three weeks post infection. Ruling out the possible presence of filterable retroviruses, a filtered supernatant did not display RT activity and did not transforms. ConclusionsWe discovered an ancestral microbial agent, acutely transforming. For its giant dimensions, the ability to retain the Gram stain, the presence of a mega-genome and its retroviral nature, we tentatively named the agent Retro-Giant-Virus (RGV). However, distinct from amoeba giant Mimiviruses, this transforming human agent has a different nature and does not require for its isolation amoeba co-culture, since amoeba is not its natural host. The morphology, biology and genetic features allocate this mammalian giant microbe halfway in between a classic oncogenic virus and an infectious cancer cell. Its transforming nature goes with its constant ability to induce tumours formation in mice.

cancer biology↗

bioRxiv2019

The Human Nickel Microbiome and its relationship to Allergy and Overweight in Women

IntroductionNickel exposure usually presents as Allergic Contact Dermatitis. However, Nickel not only causes dermatitis, but an excess of dietary Nickel is reported to be responsible for overweight, metabolic disorders and imbalance of gut microflora. ObjectiveThe aim of study is to expand a preliminary reported evidence of the presence of Nickel-resistant bacteria isolated in human microbiome and further evaluate their association with nickel allergy and overweight in females, the gender mostly affected by Nickel exposure. Materials and MethodsWe collected stool samples from 11 lean female with a nickel allergy (BMI <25) and 17 overweight nickel allergic subjects (BMI >25). 11 subjects not allergic to nickel served as control group. Stool cultures were supplemented with increasing concentrations of nickel sulphate (NiSO4*6H2O) from 0.1mM up to 50 mM, in both aerobic and anaerobic conditions (culturomics-approach Lusi, 2017). Stool cultures not supplemented with nickel were used as controls. Identification of Nickel resistant bacteria was made by MALDI-TOF technology. ResultsIn control subjects, 5 mM NiSO4 was the cut off for microbial growth. Conversely, gut bacteria continued to grow at concentration higher than 5 mM in allergic subjects. In particular, Nickel resistant bacteria able to tolerate 32 mM of NiSO4 was detected in 10% of lean allergic and 29% of overweight allergic females. Gut microbes able to grow in at extremely high NiSO4 concentration (50mM) could only be detected in overweight patients with a severe nickel allergy. At increasing NiSO4 concentration, allergic females, especially those with increased BMI, showed a progressive decrease of Enterobacteriaceae along with an increased presence of Lactobacillaceae, Bacillaceae and Clostridiaceae compared to control subjects. Major changes in microbial composition were noted at 50 mM of NiSO4 in overweight allergic females. ConclusionOverweight females with a nickel allergy harbor gut microbes highly resistant to nickel and the role of these bacterial strains must be further elucidated.

microbiology↗