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Histopathologic features of DMBA-induced mammary tumors in blind-underfed, blind-anosmic, and blind cold-exposed rats: influence of the pineal gland.

The influence of the pineal gland on the histopathologic changes induced in mammary glands by 7, 12-dimethylbenz(a)-anthracene (DMBA) has been studied. To achieve the maximum expression of pineal action in animals, 28-day-old female Sprague-Dawley rats were subjected to one of the following treatments: blindness + olfactory bulbectomy (BA), blindness + underfeeding (BU), or blindness + cold exposure (BC). Half of the rats in each group were also pinealectomized. Animals that were intact or only pinealectomized served as controls. Each animal received a single intragastrical dose of DMBA (20 mg) 4 weeks after performing the treatments mentioned above. At 28 weeks of age animals were sacrificed, and mammary tumors as well as mammary glands without macroscopic lesions were collected. Animals of the BU group failed to develop any tumors throughout the 20-week control period. In the remaining groups, tumors were found; the relation between number of adenocarcinomas (AC) and fibroadenomas was similar, always with a greater incidence of ACs. Some ACs showed areas with changes in the ductal epithelium that are considered signs of tumoral regression; pinealectomized animals had the lowest incidence of ACs with signs of regression. Ductule hyperplasia, considered as a premalignant lesion, was more frequent in pinealectomized rats than in controls and in animals with enhanced pineal function (BA, BU, and BC). Some nontumoral mammary glands showed dysplastic lesions; these lesions were less frequent in BU rats than in controls. We conclude that suppression of pineal function sensitizes the ductule cells to the initiation of neoplastic processes and hinders the development of regressive changes.

9,10-Dimethyl-1,2-benzanthracene↗

Antibodies of ovarian antigens in different diseases of the ovary.

Using the test of antiglobulin serum consumption against the human ovarian antigen, investigations were conducted on the presence of antiovarian antibodies in the blood serum of 432 women with different diseases of the ovary and 50 healthy women as control group. Autoantibodies were found in 12 of 172 patients with inflammatory lesions of the ovary (7.0%), in 18 of 118 patients with ovarian failure (15.3%), and in 21 of 65 patients with malignancies of the ovary (32.3%). No autoantibodies were detected in any of the healthy women from the control group, in any of the 10 patients with tuberculosis of the adnexa, or in any of the 67 women operated upon for benign neoplasms of the ovary. The authors formulate the suppression that there may be a correlation between the occurrence of autoantibodies, lesions of the ovarian tissue, and the malignancy of the neoplastic process.

Adnexal Diseases↗

Increase of MMP-13 expression in multi-stage oral carcinogenesis and epigallocatechin-3-gallate suppress MMP-13 expression.

BACKGROUND: Matrix metalloproteinases (MMPs) play pivotal roles in tumor progression. MMP-13 (collagenase-3) digests collagen and other extracellular components. MATERIALS AND METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and zymograph were used to study the roles of MMP-13 during the neoplastic process of oral squamous cell carcinoma (OSCC). RESULTS: Increase of MMP-13 mRNA and protein expression in OSCC cell lines relative to cultivated normal oral keratinocytes was found. MMP-13 mRNA expression in OSCC was significantly higher than in non-cancerous match tissue (NCMT) in 36 tissue pairs. Esophageal squamous cell carcinoma also exhibited high MMP-13 mRNA expression. The percentage of OSCC exhibiting strong MMP-13 immunoreactivity was significantly higher than pre-invasive lesion and NCMT. Treatment with >5 microm epigallocatechin-3-gallate (EGCG) to OEC-M1 cells suppressed the expression and activity of MMP-13. CONCLUSION: MMP-13 could be a potential tumor marker for OSCC. The effects of EGCG in tumor inhibition may act partially through the modulation of MMP-13.

Adult↗

Expression of epidermal growth factor receptor in human meningiomas and meningeal tissue.

The aim of this study was to examine meningeal tissue under normal, reactive, and neoplastic conditions for expression of epidermal growth factor receptor (EGFR) using an improved histochemical method, namely biotinylated epidermal growth factor. EGFR was found in all the examined meningiomas (12 benign and three anaplastic) and in neonatal rat meninges, whereas normal and injured adult human and rat meninges did not exhibit detectable EGFR. These observations indicate that EGFR is involved in the development of meningeal tissue. Further, EGFR is abnormally expressed in meningeal tumours, indicating a role of EGFR in the neoplastic process of these tumours. The regular expression of EGFR in human meningiomas suggests EGFR as a tumour marker for this tumour type.

Adult↗

Review of the technique and complications of median sternotomy in the dog and cat.

The surgical and medical records of 67 dogs and nine cats which underwent median sternotomy over a five-year period were reviewed. The indication for median sternotomy and the short and longer term complications were recorded. Twenty-six of the dogs died or were euthanased within 48 hours of the surgery as a consequence of the pre-existing disease or complications of the intrathoracic surgical procedure. A further four dogs were enthanased between 48 hours and 14 days following confirmation of neoplastic processes. Thirty-seven dogs were alive at 14 days: of these, seven dogs (19 per cent) experienced short-term wound complications, including haemorrhage, wound infection, thoracic limb neurological deficits and excessive postoperative discomfort. Of the 37 dogs alive for longer term follow-up, eight dogs (22 per cent) experienced wound complications, including haemorrhage, sternal fracture, sternal osteomyelitis and delayed wound healing. No complications were noted in the cats.

Animals↗

Osteosarcoma following total hip arthroplasty in a dog.

Osteosarcoma involving the distal right femur was diagnosed in a nine-year-old female neutered Rottweiler seven years after total hip arthroplasty had been performed on that limb. The findings were consistent with a primary bone tumour and pathological fracture of the right femoral condyle with loosening of the orthopaedic implant and fracture of the polymethylmethacrylate at the distal aspect of the femoral component. Possible hypotheses to explain the association of osteosarcoma with total hip arthroplasty suggest that the neoplastic process was the result of some derangement of host tissue and the healing process or that the implants or their by-products were carcinogenic. Given the large number of total hip arthroplasties that are routinely performed in dogs, the development of a malignant lesion appears to be an extraordinary complication and may be completely coincidental.

Animals↗

Thoracic high-resolution computed tomography in the diagnosis of metastatic carcinoma.

Three dogs were presented for investigation of recurrent pyrexia of unknown origin, chronic vomiting and respiratory distress, respectively. One dog was markedly underweight and the other two were cachexic. Physical examination and initial diagnostic tests failed to establish the underlying cause of the presenting signs. Thoracic radiographs were within normal limits for the age of the dog. In each case there was a high index of suspicion for an occult neoplastic process in view of the profound unexplained weight loss present. High-resolution computed tomography (HRCT) of the thorax was performed. The lung fields were divided into three zones for analysis and a novel classification scheme was used to describe the HRCT findings in each zone. Postmortem examination and histopathology confirmed the presence of an infiltrating metastatic carcinoma in all three cases. The HRCT changes correlated closely with the pathological findings. The authors conclude that HRCT of the lung should be considered for pulmonary metastatic screening in the dog and introduce a classification system for HRCT findings, based on terminology used in human medicine.

Adrenal Gland Neoplasms↗

Observations on the carcinogenicity of asbestos fibers.

This paper summarizes animal experiments and in vitro data carried out to study the oncogenic effects of asbestos fibers on mesothelial cells. An interpretation of the results is made in light of current statements on the carcinogenicity of asbestos fibers. Experimental results appear to show that the carcinogenicity of mineral fibers is a complex, multiparametric phenomenon. Chromosomal mutations and possibly oxygen derivatives are involved in the genesis of the fiber-induced neoplastic process and may be the result of the intrinsic fiber properties, size, and physicochemistry. The role of fiber solubility is discussed; it is suggested that additional experiments are necessary for a better understanding of the importance of solubility in the concept of biopersistence.

Animals↗

Mesotheliomas due to asbestos used in railroads in Italy.

The available knowledge of the oncogenic risks of asbestos, the presentation of some data on the uses of asbestos in railroads, with particular regard to the Italian State Railroads (Ferrovie dello Stato = FS), and the identification of groups at risk because of exposure to asbestos used in railroads are briefly reviewed. The available data in the literature on the pathologic effects of such exposure, and in particular on the onset of mesotheliomas among machinists and other railroad workers, are also summarized. Eighty-three cases, in various Italian regions, of mesothelioma (78 pleural, 4, peritoneal, and 1 pericardial) are reported that are related to the exposure to asbestos used in railroads. Twenty-six of these cases (among which 25 were reported in the Emilia-Romagna region) were submitted to a detailed study at the Bologna Institute of Oncology. Forty-nine cases of mesothelioma occurred among FS workers, in particular machinists; 29 cases occurred among machinists of rolling-stock workshops not belonging to the FS; 3 cases occurred among travelling workers of rolling-stock not belonging to the FS; 2 cases were found in members of the family (a daughter and a wife) of FS workers. This series of cases, together with similar data from the literature, proves the existence and gravity of an actual health risk due to asbestos used in the railroads. On the basis of the available data, the following steps are considered necessary: the adoption of preventive measures, the performance of medical oncological surveillance, the promotion of systematic epidemiologic investigations, and, finally, the placement of greater emphasis on basic research, aimed at generating information on the biological events taking place during the incubation period of the tumors. This information, hopefully, could be used to reduce the biological effect of exposure, and therefore for controlling the neoplastic process before onset of the disease in those who, having been exposed, although healthy, are potentially at risk.

Epidemiologic Methods↗

Multi-modal medical image integration to optimize radiotherapy planning in lung cancer treatment.

This work presents a method for CT and PET image registration, and multi-modal analysis, to optimize radiotherapy planning in lung cancer treatment. The method relies on an image registration technique based on fiducial external markers to realign, spatially, PET images with the CT spatial reference system. The method was set up for clinical use in radiotherapy, allowing minimal modifications to be introduced in the management of patients undergoing radiation treatment. The accuracy of the registration technique was evaluated on patient studies in terms of Target Registration Error and was found to be less than 6.40 mm. The method was applied in the treatment planning of five patients affected by non-small-cell lung cancer, revealing the usefulness of PET/CT integration in delineating the extension of both the tumor mass and the tissues involved in the neoplastic process. Moreover, the functional information provided by PET often led to alterations in the treatment planning, changing the size and/or direction of radiation portals. The proposed method for PET/CT integration has been confirmed as being useful for optimizing radiotherapy planning in lung cancer treatment.

Algorithms↗

The consensus coding sequences of human breast and colorectal cancers.

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of approximately 90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention, and open fertile avenues for basic research in tumor biology.

Amino Acid Substitution↗

A novel putative tyrosine kinase receptor encoded by the eph gene.

Growth factors and their receptors are involved in the regulation of cell proliferation and also play a key role in oncogenesis. In this study, a novel putative kinase receptor gene, termed eph, has been identified and characterized by molecular cloning. Its primary structure is similar to that of tyrosine kinase receptors thus far cloned and includes a cysteine-rich region in the extracellular domain. However, other features of the sequence distinguish the eph gene product from known receptors with tyrosine kinase activity. Thus the eph protein may define a new class of these molecules. The eph gene is overexpressed in several human carcinomas, suggesting that this gene may be involved in the neoplastic process of some tumors.

Amino Acid Sequence↗

Recovery of uncommon bacteria from blood: association with neoplastic disease.

Table 6 is a summary of the organisms discussed with a listing of the environmental source, the endogenous source, the predisposing factors including neoplasms, and the postulated mechanisms by which the organism can gain access to the circulation. The evidence considered indicates that the entrance of one of these microorganisms into the bloodstream of a human being depends on the presence of multiplicity of predisposing factors. In the majority of cases of bacteremia due to one of these unusual organisms, two or more predisposing factors are present. Certain predisposing factors, such as cancer chemotherapy or intravenous catheterization, often provide a barrier break, while others, such as liver disease, may render the host immune system less capable of clearing organisms from the circulation. For organisms such as Campy-lobacter, Listeria, and Salmonella spp., attributes that allow the invasion of a healthy host are present and seem to be enhanced by the simultaneous presence of a predisposing condition, such as liver disease, in the host. Although somewhat fragmentary, a number of individual case reports describe bacteremia due to one of these organisms occurring weeks to years after surgery and after other therapeutic measures had effected a supposed cure of a cancer. It may be speculated that cancer patients, even after a cure, are still susceptible to bloodstream invasion by one of the aforementioned organisms by virtue of the presence of one or more predisposing metabolic, physiologic, or immunologic factors, even though these factors may be cryptic. The predominance of hematologic malignancies among cases of bacteremia due to these unusual organisms is also apparent. Although, as pointed out by Keusch (169), the reduction in the performance of immune function in hematologic malignancies compared with solid tumors is likely to be responsible, other associations of certain organisms with specific neoplasms warrant further examination. The frequency of bloodstream infections of Salmonella typhimurium and Capno-cytophaga canimorsus in Hodgkin's disease patients seems likely due to a particular mechanism which infection by these species is favored. The specific nature of these mechanisms remains to be determined. The recovery of any unusual bacterium from blood should warrant a careful consideration of the possibility of underlying disease, especially cancer. Microbiologists should advise clinicians of the unusual nature of the identified organism and provide the counsel that certain neoplastic processes, often accompanied by neutropenia, render the human host susceptible to invasion by almost any bacterium. The recovery of such organisms as C. septicum or S. bovis should prompt the clinician to aggressively seek to identify an occult neoplasm if one has not yet been diagnosed.

Bacteremia↗

Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.

The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.

Animals↗

Molecular cloning and characterization of plastin, a human leukocyte protein expressed in transformed human fibroblasts.

The phosphoprotein plastin was originally identified as an abundant transformation-induced polypeptide of chemically transformed neoplastic human fibroblasts. This abundant protein is normally expressed only in leukocytes, suggesting that it may play a role in hemopoietic cell differentiation. Protein microsequencing of plastin purified from leukemic T lymphocytes by high-resolution two-dimensional gel electrophoresis produced eight internal oligopeptide sequences. An oligodeoxynucleotide probe corresponding to one of the oligopeptides was used to clone cDNAs from transformed human fibroblasts that encoded the seven other oligopeptides predicted for human plastin. Sequencing and characterization of two cloned cDNAs revealed the existence of two distinct, but closely related, isoforms of plastin--l-plastin, which is expressed in leukocytes and transformed fibroblasts, and t-plastin, which is expressed in normal cells of solid tissues and transformed fibroblasts. The leukocyte isoform l-plastin is expressed in a diverse variety of human tumor cell lines, suggesting that it may be involved in the neoplastic process of some solid human tumors.

Amino Acid Sequence↗

Increased expression of humanin peptide in diffuse-type pigmented villonodular synovitis: implication of its mitochondrial abnormality.

OBJECTIVES: To define the pathogenesis of pigmented villonodular synovitis (PVNS), by searching for highly expressed genes in primary synovial cells from patients with PVNS. METHODS: A combination of subtraction cloning and Southern colony hybridisation was used to detect highly expressed genes in PVNS in comparison with rheumatoid synovial cells. Northern hybridisation was performed to confirm the differential expression of the humanin gene in PVNS. Expression of the humanin peptide was analysed by western blotting and immunohistochemistry. Electron microscopic immunohistochemistry was performed to investigate the distribution of this peptide within the cell. RESULTS: 68 highly expressed genes were identified in PVNS. Humanin genes were strongly expressed in diffuse-type PVNS, but were barely detected in nodular-type PVNS, rheumatoid arthritis, or osteoarthritis. Humanin peptide was identified in synovium from diffuse-type PVNS, and most of the positive cells were distributed in the deep layer of the synovial tissue. Double staining with anti-humanin and anti-heat shock protein 60 showed that humanin was expressed mainly in mitochondria. Electron microscopy disclosed immunolocalisation of this peptide, predominantly around dense iron deposits within the siderosome. CONCLUSIONS: Increased expression of the humanin peptide in mitochondria and siderosomes is characteristic of synovial cells from diffuse-type PVNS. Humanin is an anti-apoptotic peptide which is encoded in the mitochondrial genome. Present findings suggest that mitochondrial dysfunction may be the principal factor in pathogenesis of diffuse-type PVNS and that humanin peptide may play a part in the neoplastic process in this form of PVNS.

Arthritis, Rheumatoid↗

Erosive spondylopathy.

Seven patients with chronic dorsolumbar pain, stiffness and some restriction of spinal movements are described. Multiple lesions of the vertebral bodies were present. The lesions occurred at various levels and all had similar radiological characteristics, often returning to normal after several years. Vertebral changes of this type may be seen in patients with ankylosing spondylitis but for a variety of cogent reasons presented in this report our patients did not readily fall into this diagnostic group. The aetiology of these vertebral lesions is unknown but available evidence indicates that they should not be attributed to an infectious or neoplastic process.

Adult↗

Endometriosis and the gut.

Six patients with endometriosis involving the intestine are described and illustrate the variety of symptoms which may occur in this condition, many of which are frequently associated with the more common gastrointestinal illnesses. A correct preoperative diagnosis based on history, clinical examination, radiology, and endoscopy may be difficult to make, and when first discovered at laparotomy endometriosis can easily be mistaken for other inflammatory, or neoplastic processes. A histological diagnosis should always be made before definitive treatment.

Adult↗