Skin Epitheliomas Research Articles

How many Italian cancer patients are eligible for, and may respond to, Italian Medicines Agency-approved immune checkpoint inhibitors?

This cross-sectional study was aimed at estimating the number of Italian incident cancer patients in 2020 eligible for, and respondent to, immune checkpoint inhibitors (ICI). The study is based on publicly available data: the ICI approved until August 2022 by the Italian Medicines Agency (AIFA) with their specific indications and overall observed responses, rther details can be found in the Online Supplementary Materi cancer incidence estimates at 2020 and observed cancer deaths, and published papers with estimates on the frequency of different cancer stage/histology/markers etc. corresponding to AIFA authorizations. In the analyzed period, a total of seven ICI were authorized in Italy for 20 cancer types. The estimated number of ICI-eligible patients in 2020 was 48,400, 14.3% of those tumors (including skin epitheliomas) that may fit AIFA-indications, and 10.5% of all the incident malignant tumors, including skin epitheliomas. The number of patients who may benefit from ICI therapy was 24,052, 49.7% of the ICI-eligible ones, or 5.2% of the overall estimated incident cancers in 2020. In conclusion, although the number of ICI-eligible patients is a relatively small proportion of the yearly burden of cancers, about half of them may respond to ICI-treatment.

Efficacy of High-Ozonide Oil in Prevention of Cancer Relapses Mechanisms and Clinical Evidence.

Simple SummaryCancer relapses after chemo-radiotherapies arise from cancer stem cells able to escape cell killing because of their high antioxidants level. The aim of this study was to test the efficacy of ozonized oils to decrease the rate of cancer relapses. In vitro, oils at high ozonide content penetrate inside cancer cells releasing oxygen and reactive oxygen species damaging the thin outer membrane of inactive mitochondria. This event triggers intracellular calcium release and activates apoptosis. In vivo, ozonized oil has been administered by the oral route effectively decreasing blood antioxidants in cancer patients. This approach results in significant increase of survival rate and decrease of relapses in 115 cancer patients (brain, lung, pancreas, colon, skin) undergoing standard radio-chemotherapy regimens during a 4-years follow up. Obtained results indicate that the administration of ozonized oil represents an integrated approach to decrease the risk of radio-chemoresistance and cancer relapses in cancer patients.Background: Cancer tissue is characterized by low oxygen availability triggering neo angiogenesis and metastatisation. Accordingly, oxidation is a possible strategy for counteracting cancer progression and relapses. Previous studies used ozone gas, administered by invasive methods, both in experimental animals and clinical studies, transiently decreasing cancer growth. This study evaluated the effect of ozonized oils (administered either topically or orally) on cancer, exploring triggered molecular mechanisms. Methods: In vitro, in lung and glioblastoma cancer cells, ozonized oils having a high ozonide content suppressed cancer cell viability by triggering mitochondrial damage, intracellular calcium release, and apoptosis. In vivo, a total of 115 cancer patients (age 58 ± 14 years; 44 males, 71 females) were treated with ozonized oil as complementary therapy in addition to standard chemo/radio therapeutic regimens for up to 4 years. Results: Cancer diagnoses were brain glioblastoma, pancreas adenocarcinoma, skin epithelioma, lung cancer (small and non-small cell lung cancer), colon adenocarcinoma, breast cancer, prostate adenocarcinoma. Survival rate was significantly improved in cancer patients receiving HOO as integrative therapy as compared with those receiving standard treatment only. Conclusions: These results indicate that ozonized oils at high ozonide may represent an innovation in complementary cancer therapy worthy of further clinical studies.

Temoporfin PDT partial response of multiple head-and-neck skin epitheliomas: Implication of warfarin

Temoporfin PDT partial response of multiple head-and-neck skin epitheliomas: Implication of warfarin

Temoporfin PDT partial response of multiple head-and-neck skin epitheliomas: Implication of warfarin

Temoporfin PDT partial response of multiple head-and-neck skin epitheliomas: Implication of warfarin

High-dose-rate brachytherapy in a large squamous cell carcinoma of the hand

Purpose High-dose-rate 192Ir-based brachytherapy can be used as an exclusive treatment of large skin tumors when teletherapy or surgery is not feasible. A case of an extended inoperable skin epithelioma of the hand is reported; the lesion involved the first finger, the tenar, the palm, and the back. Methods and materials A detailed description of an individual case is reported. A customized mold was created for the patient, to administer a fractionated brachytherapy treatment in a reproducible way. Results A total dose of 50 Gy was administered in 10 fractions, after a time schedule of three fractions per week. The treatment was well tolerated and the acute effects (mainly, epitheliolysis) were resolved completely within a month after the treatment. Conclusions Nine months after the treatment, the malignant lesion completely disappeared and the cosmetic results are quite satisfactory. Therefore, we conclude that the treatment technique is well adaptable to any particular geometry and that the fractionation scheme has proven to be well tolerated and effective in tumor eradication.

Population-based incidence and mortality cancer trends (1986–1997) from the network of Italian cancer registries

The objective of this study was to analyse incidence and mortality cancer trends in the Italian Network of Cancer Registries (about 8,000,000 inhabitants) during the period 1986-1997. Included were 525,645 newly diagnosed cancers and 269,902 cancer deaths (subjects > 14 years). Joinpoints (points in time where trend significantly changes from linearity) were found and estimated annual percentage changes (EAPC) used to summarize tendencies. Overall cancer incidence increased in both sexes and cancer mortality significantly decreased (since 1991 among men). Lung cancer showed significantly decreasing incidence (EAPC = -1.4%) and mortality (EAPC = -1.6%) among men and increasing trends among women. In women, breast cancer incidence significantly increased (EAPC= +1.7%) and mortality decreased since 1989 (EAPC= -2.0%). Stomach cancer incidence and mortality decreased in both sexes. Prostate incidence sharply increased since 1991 and mortality decreased. Colon cancer incidence increased and rectum mortality decreased significantly in both sexes. Significant increases in incidence were also found for kidney (up to 1991 among men), urinary bladder, skin epithelioma, melanoma, liver (up to 1993 among men), pancreas, mesothelioma, Kaposi's sarcoma (up to 1995 among men), testis, thyroid, non-Hodgkin's lymphomas and multiple myeloma. Mortality significantly decreased for cancers of the oral cavity and pharynx, oesophagus, liver (women), larynx (men), bone, cervix (since 1990), central nervous system, urinary bladder, thyroid, Hodgkin's lymphomas and leukaemias (men). Non-Hodgkin's lymphoma mortality increased in both sexes. In conclusion, most of the changes seen can be explained as the effect of changes in smoking habits and of the extension of secondary prevention activities. The Italian health care system will also have to cope with growing cancer diagnostic and therapeutic needs due to population ageing.

The hamster polyomavirus--a brief review of recent knowledge.

The hamster polyomavirus (HaPV) was first described in 1967 as a virus associated with skin epithelioma of the Syrian hamster. The tumors appear spontaneously in a hamster colony bred in Berlin-Buch (HaB). Virus particles isolated from skin epitheliomas cause lymphoma and leukemia when injected into newborn hamsters from a distinct colony bred in Potsdam, Germany (HaP). The viral genome has been totally sequenced and the overall genetic organization establishes HaPV as a member of the polyomaviruses. HaPV is a second example of an middle T (MT) antigen encoding polyomavirus and nucleotide sequence homologies designates the mouse polyomavirus (Py) as the closest relative. Lymphomas induced by HaPV in HaP hamsters do not contain virus particles but instead accumulate different amounts of nonrandomly deleted free and/or integrated viral genomes. Transgenic mice produced by microinjection of HaPV DNA into the pronucleus of fertilized eggs of Gat: NMRI mice developed both, epitheliomas and lymphomas. Both tumor types contain extrachromosomal DNA. HaPV DNA was found to replicate in hamster lymphoid and fibroblast cell lines. Fully reproductive cycles could be detected only in GD36 lymphoblastic leukemia cells. HaPV carries the full transforming properties of a polyomavirus in vitro. Immortalization of primary rat cells is essentially carried out by the HaPV large T (LT) antigen and coexpression of HaPV MT and HaPV small T (ST) antigen is required for full transformation of rat fibroblasts. The preferential binding of HaPV MT to c-Fyn, a Src family kinase, has been proposed as a mechanism leading to lymphoid malignancies. Heterologous expression of HaPV-VP1 allowed the formation of virus like particles (VLPs) resembling HaPV particles. The high flexibility of HaPV-VP1 for insertion of foreign peptides offers a broad range of potential applications, especially in vaccine development.

Cancer Prevalence in the Elderly

To describe the cancer prevalence in elderly Italian people and analyze the differences, if any, with the prevalence among younger subjects. The cancer prevalence among elderly patients (65 years and over), the three age classes encompassing elderly age (65-74 years, 75-84 years, 85 years and over) and younger patients (0-64 years) was computed using the PREVAL method on the basis of the incident cases over the period 1976-1992 followed up to 31 December 1992 (prevalence reference date). Data were collected by 11 Italian cancer registries. The observed prevalence figures for all cancers (except skin epitheliomas), both sexes combined and considering the whole elderly group, were 1,090 and 3,601 cases per 100,000 one and five years since diagnosis, respectively; the prevalence increased up to the 75-84 age group and showed a slight decrease after age 85. With regard to specific cancer sites, in men bladder and prostate had the highest prevalence 5 years from diagnosis (more than 800 cases per 100,000), followed by colon and lung (about 500 cases per 100,000) stomach and rectum (about 300 cases per 100,000); in women breast cancer ranked first (more than 1,000 cases per 100,000), followed by colon (about 350 cases per 100,000), corpus uteri, stomach and rectum cancers (between 150 and 200 cases per 100,000). For all malignancies and the two sexes combined the prevalence figures were about six times higher in the older than in the younger age group. These figures confirm the important role of aging in determining the increase in cancer prevalence. The resulting prevalence figures clearly indicate the cancer burden placed on health care services; moreover, the figures will probably increase in the next decades due to a possible improvement in survival and to the dramatic aging of the population, assuming a stable trend for incidence rates. This picture will represent a major challenge for politicians and those dealing with health care planning and social policies in general, especially in the light of the reduction of the available financial resources and the specific features of medical and social needs in the elderly.

Synchronous and metachronous diagnosis of multiple primary cancers.

In the time period near to the diagnosis of a new cancer, other tumors (synchronous cancers), especially slow-growing tumors, may be detected because several diagnostic examinations are performed. The frequency of synchronous in comparison with metachronous carcinomas has been evaluated in a population-based series of multiple primary cancers. The case series of multiple primary cancers of the Tuscany Tumor Registry, incident during the period 1985-1991 was analyzed. For each site of a second independent tumor, the proportions of synchronous (diagnosed within 2 months of the first primary) and metachronous cancers were compared with the mean distribution (all sites except the specific one). During 1985-1991, 1095 patients had two independent tumors diagnosed; 216 were synchronous. The proportion of synchronous compared to metachronous cancers was significantly higher for bladder, prostate and renal cell carcinomas; it was significantly lower for lung cancer. When cancers following skin epitheliomas were evaluated, only the proportion of synchronous skin cancers was significantly increased. Silent slow-growing tumors are suspected to be more frequent in patients with prostate, bladder or renal cell carcinomas. In fact, they were most frequently diagnosed during ascertainment for another cancer. When few examinations were performed, as after the diagnosis of a skin epithelioma, no difference between metachronous and synchronous cancers was evident, except for skin.

Hamster polyomavirus-encoded proteins: gene cloning, heterologous expression and immunoreactivity.

The hamster polyomavirus (HaPV) is associated with spontaneously appearing skin epithelioma of the Syrian hamster Z3 strain. Virus particles prepared from the skin epithelioma cause lymphoma and leukemia when injected into newborn hamsters from a distinct Syrian hamster colony (HaP); in contrast to the skin epithelioma the hemopoietic tumors are virus free but accumulate viral DNA. To study the humoral immune response of HaPV-infected Z3 hamsters we produced recombinant HaPV proteins in Escherichia coli as beta-galactosidase-, TrpE- and dihydrofolate reductase-fusion proteins or as non-fused proteins. Recombinant plasmids carried segments of all putative early and late HaPV proteins. The recombinant proteins were detected in stained SDS polyacrylamide gels and in Western blots using monoclonal anti-TrpE and anti-beta-galactosidase antibodies and sera of HaPV-infected hamsters. Sera from HaPV-infected Z3 hamsters and crude lysates of all clones were applied to Western blots to characterize the humoral immune response in the animals. HaPV-specific antibodies were found to be directed against early protein segments translated from the first common exon and from the second unique exon of LT and MT, resp., as well as against the late proteins VP1 and VP2/3. The almost complete VP2 was recognized by all sera whereas VP1 was detected only by a half of the sera. Our data suggest the presence of at least 2 immunodominant regions in VP2, one in the C-terminal VP1 and at least 4 in early proteins.

Induction of lymphomas by the hamster papovavirus correlates with massive replication of nonrandomly deleted extrachromosomal viral genomes

The hamster papovavirus isolated from skin epithelioma can induce lymphomas and leukemias after subcutaneous inoculation into newborn hamsters. The lymphoma cells are virus free but contain large amounts of extrachromosomal hamster papovavirus DNA. We have cloned and partly sequenced some of these DNA molecules from independent tumors. These genomes displayed overlapping deletions consistently sharing a common end within the noncoding regulatory sequences; the other end was variable but always extended into the sequence coding for the N-terminal part of the viral capsid VP2. This unique in vivo interaction between a polyomavirus and its cellular host, the genesis of these variant molecules, and their role in the lymphoma formation are discussed.

Post-burn squamous cell cancers in Nigerians

Eighteen patients with post-burn skin cancers seen at Enugu over an 8-year period have been reviewed. All the tumours were well differentiated squamous cell carcinomas. The mean age of the patients was 36 years and the incubation period of 17.5 years was shorter than in previously reported studies. An aggressive policy in the treatment of these tumours by surgery alone has resulted in an 87% 5-year survival rate for lower limb tumours. When secondary tumours due to pre-existing dermatological diseases are excluded, post-burn skin epitheliomas constituted the largest group of squamous cell skin cancers seen in Enugu, Nigeria.

Trace elements in skin epitheliomas

Skin tissue samples from 41 patients suffering from skin epitheliomas were analyzed by the PIXE method. Skin samples from the non-affected areas and blood serum were also analyzed for the same patients. The elements determined were K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Br, Rb, and Pb. Their concentrations in the healthy skin and the serum were normal. The concentrations in the lesions were nearly the same for both basal cell and squamus cell epitheliomas (BCE and SCC) except for higher zinc and lower bromine values in the BCE samples. However, substantial differences were observed between the affected and non-affected skin.

Papovavirus in Epitheliomas Appearing on Lymphoma-Bearing Hamsters: Lack of Association With Horizontally Transmitted Lymphomas of Syrian Hamsters<xref ref-type="fn" rid="FN2">2</xref>

Several epizootics of lymphoma occurred in a colony of LVG hamsters contaminated with an unusual, horizontally transmitted, subviral, lymphomagenic agent. Hamsters with horizontally transmitted lymphoma, or others housed with these hamsters, occasionally developed epitheliomas bearing an unclassified papovavirus. The possibility that the virus present in the wart-like structures in our hamster colony could activate lymphoma was tested, and a search was conducted for mature virions in passaged epitheliomas and lymphomas. The agent responsible for the skin epitheliomas in our hamster facility was an icosahedral, 36-nm virion compatible with the morphology of a polyomavirus or simian virus 40. Horizontally transmitted lymphoma cells and epitheliomas contained hamster papovavirus (HaPV) DNA sequences detected by dot hybridization; however, such sequences were not found in extracts of lymphomas with oncogenic potential. In contrast to reports by other investigators, infection of hamsters with the papovavirus present in primary epitheliomas produced epitheliomas in good yield but was not reproducibly associated with lymphoma induction. These data confirm the observation that the HaPV is the causative agent of epitheliomas, but they suggest clearly that HaPV is not the agent responsible for lymphomagenesis.

A new member of the polyomavirus family: the hamster papovavirus. Complete nucleotide sequence and transformation properties.

The hamster papovavirus (HapV) is associated with multiple skin epitheliomas of the Syrian hamster. We have sequenced its genome. It is a double-stranded circular DNA of 5366 bp. The hypothetical genomic organization deduced from this nucleotide sequence is clearly of the polyoma type with the two strands coding in the opposite directions from a noncoding region that shows some of the features of a replication origin and a transcription control region. The amino acid sequences predicted from the open reading frames show an average of 50% homology with polyoma-coded polypeptides. The HapV is, after polyoma, the second example of a papovavirus coding for a middle T antigen. The cloned DNA can immortalize primary rat embryo cells and transform an established rat cell line. The viral DNA is stably integrated into the host genome.

Skin cancer in renal transplants

Malignant skin tumours are more common following renal transplants. Squamous cell carcinomas (S.C.C.) are increased, in contrast to B.C.C. Kerato acanthomas (K.A.) were increased and showed a marked tendency to recur and appeared more aggressive than S.C.C.'s. Azathioprinc appears to be more likely to cause skin cancer than chlorambucil. This increase in skin epitheliomas may be due to a failure of endonuclease repair of DNA. Psoriatics appear to be less likely to develop these lesions.

INDUCTION OF TRANSMISSIBLE LYMPHOMAS IN SYRIAN HAMSTERS BY APPLICATION OF DNA FROM VIRAL HAMSTER PAPOVAVIRUS-INDUCED TUMORS AND BY CELL-FREE FILTRATES FROM HUMAN TUMORS

DNA isolated from skin epitheliomas containing papovavirus induced lymphomas within four to eight weeks in 40 to 50 per cent of newborn Syrian hamsters injected. This DNA effect was eliminated by DNase but not by RNase and was not induced by DNA preparations of transplanted epitheliomas or the induced lymphomas. Lymphomas were similarly induced by cellfree filtrates from certain human tumors such as gastric carcinomas and ovarian tumors. Little or no lymphoma effects were observed following injections with filtrates derived from normal human or animal tissues or human blood. The lymphomas induced by DNA and human tumors were transmissible by cell-free filtrates to newborn Syrian hamsters; however, successful serial passage, like the primary lymphomas induced by the DNA preparations, depended upon the use of a newborn hamster from a special breeding colony of hamsters.

A practical time-dose formula for x-ray therapy of skin cancer.

A simplified equation has been derived from previous data (von Essen 1960; 1963) in order to facilitate the slide-rule computation of dose-time factors for the single field X-radiation treatment of skin epitheliomas. This equation relates skin tolerance to the curative dose as a function of radiation depth dose, area and overall time, based on five or six treatments a week.

A New Family of Potent Carcinogens : Benzopyridocarbazoles

ALTHOUGH the introduction of heterocyclic nitrogen atoms in the molecules of polycyclic compounds sometimes decreases carcinogenic activity (for example, the inactive pyrenoline as compared with 3,4-dibenzopyrene1), there are many instances in which the carcinogenic potency is thereby maintained or even enhanced. Such is the case with the angular benzacridines2, some of which are more active than the corresponding 1,2-benzanthracenes in respect of induction of skin epitheliomas and sarcomas, and with the inactive pentacene, in the molecule of which the introduction of two nuclear nitrogen atoms leads to the sarcoma-producing dinaphthazine3. In view of the already established carcinogenic activity of the angular dibenzocarbazoles4, it was interesting to examine the biological properties of the recently synthesized aza derivatives5.

Thorium X treatment of skin epithelioma, keratoses, and delayed radiation changes.

Epitheliomas, as well as keratoses and superficial radiation injuries, can be successfully eradicated by applying thorium X in solution or in an ointment, the effect being due apparently to the intense ionizing properties of the alpha particle. Unsatisfactory sequelae such as ugly scarring, keloid formation, depigmentation, telangiectasis, or other untoward radiation effects have not been observed to date. Thorium X should not be confused with thorium or thorium compounds. The thorium paste used by Bulkley (1) did not contain thorium X but thorium oxide in combination with other chemicals. The action of this paste was mainly a caustic one, not dependent on its radioactive qualities. History Due to scarcity of radium in Germany, investigators turned to mesothorium as a source of radiation energy. As early as 1912 independent reports by Bickel (2) and Pappenheim (3) appeared in the German literature. Both referred to the oral administration of thorium X in the treatment of anemia and leukemia. The following year Naegeli and Jessner (4) reported on the efficacy of the external application of thorium X in the treatment of psoriasis, neurodermatitis, lupus erythematosus, and lupus vulgaris. Further work dealing with the local application of thorium X in chronic dermatoses was carried out by Fabry (5, 6, 7), Jadassohn (8), Nagelschmidt (9), Pinkus (10), and Prosser Thomas (11). In reporting his experiences with thorium X in the treatment of nevus flammeus (port-wine mark) and various dermatoses, Prosser Thomas indicated that he had also successfully treated several of the flat, cicatrizing superficial basal-cell lesions. He is therefore to be regarded as the pioneer in the treatment of skin epithelioma by this means. Except for the workers listed above, all those reporting on the use of thorium X have described its application in needles with various filtration, simulating radium and radon therapy technics. When thorium X is thus enclosed in a metal sheath, the beta and gamma factors only are utilized, and as some 99 per cent of the energy emitted is in the form of alpha particles, immeasurably larger amounts are necessary to produce any biological effect. The needles used contained 500 μc. (micocuries) or 0.5 mc. of thorium X per centimeter of length, on the basis of Halber-staedter's (12) researches in 1923. Alpha rays from radon have been utilized by Uhlmann (13), Low-Beer and Stone (14), and others. They kneaded radon gas into a vaseline base to treat post-irradiation skin injuries and have reported good results. The concentration of radon ranged from 17 to 34 μc. (50–100 e.s.u.) per gram of vaseline. Uhlmann contended that the healing effects observed were due to stimulation of the epithelial cells as a result of alpha particle bombardment.