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Model systems for the study of prostatic cancer.

Application of suitable in vivo and in vitro model systems are necessary to further investigations in prostatic adenocarcinoma. Model systems are defined, and discussed in terms of their potential application to the study of the neoplastic process.

Adenocarcinoma↗

Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is overexpressed in many transplantable animal and autochtonous human cancers, in healing wounds, and in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. All of these entities are characterized by angiogenesis, altered extracellular matrix, and variable degrees of hypoxia. In addition, two VPF/VEGF receptors, flt-1 and kdr, are overexpressed by endothelial cells that line the microvessels that supply these tumors/inflammatory reactions. On the basis of these and other data, we have proposed a model of angiogenesis in which VPF/VEGF plays a central role: this model is applicable to tumors and also to the angiogenesis that occurs in non-neoplastic processes.

Animals↗

Coccidioidomycosis osteomyelitis masquerading as a bone tumor. A report of 2 cases.

BACKGROUND: Coccidioidomycosis involving the lung is common in endemic areas. However, it is unusual for it to present as a solitary bone lesion. CASES: Two cases of Coccidioides immitis osteomyelitis clinically and radiographically mimicked a primary bone tumor. Fine needle aspiration (FNA) biopsy of these lytic bone lesions yielded diagnostic material. Aspirated material in 1 case showed a suppurative, granulomatous inflammation and scattered spherules with refractile walls, some containing endospores consistent with coccidioidomycosis. Smears in the other case showed acute inflammation and necrosis, and rare spherules were identified with the Gomori-mathenamine-silver stain. C immitis infection was confirmed by culture in both cases. CONCLUSION: Although rare, coccidioidomycosis can involve the bone and mimic a primary bone tumor. FNA biopsy is helpful in differentiating between inflammatory and neoplastic processes involving bone by acquiring material for cytologic studies and cultures.

Adult↗

Summary statement on quantitative cytochemistry (DNA and molecular biology): Task Force 8.

OBJECTIVE: To reach consensus on the application of quantitative cytochemical analysis of chromosomal and DNA aneuploidy in cervical cytopathology. CONCLUSION: The current Pap test has limited specificity to predict cancer and its truly progressive pre-malignant lesions. Infection with human papillomavirus may trigger genetic instability, hyperproliferation and immortalization of the cervical mucosa and cause cervical cancer. Several related molecular markers have been shown to be informative about this neoplastic process. Quantitative analysis of chromosomal and DNA aneuploidy has been shown to be an important tool for identifying (progression to) high grade squamous intraepithelial lesions. A high degree of standardization (material handling, calibration and quality control, measurement and interpretation of results) is required for accurate and reproducible measurements. Areas for further study are presented.

Aneuploidy↗

Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.

Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve.

Antibodies, Monoclonal↗

MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype.

Increased protein kinase C (PKC) activity in malignant breast tissue and positive correlations between PKC activity and expression of a more aggressive phenotype in breast cancer cell lines suggest a role for this signal transduction pathway in the pathogenesis and/or progression of breast cancer. To examine the role of PKC in the progression of breast cancer, human MCF-7 breast cancer cells were transfected with PKC-alpha, and a group of heterogenous cells stably overexpressing PKC-alpha were isolated (MCF-7-PKC-alpha). MCF-7-PKC-alpha cells expressed fivefold higher levels of PKC-alpha as compared to parental or vector-transfected MCF-7 cells. MCF-7-PKC-alpha cells also displayed a substantial increase in endogenous expression of PKC-beta and decreases in expression of the novel delta- and eta-PKC isoforms. MCF-7-PKC-alpha cells displayed an enhanced proliferative rate, anchorage-independent growth, dramatic morphologic alterations including loss of an epithelioid appearance, and increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells exhibited a significant reduction in estrogen receptor expression and decreases in estrogen-dependent gene expression. These findings suggest that the PKC pathway may modulate progression of breast cancer to a more aggressive neoplastic process.

Animals↗

Monoclonal endothelial cell proliferation is present in primary but not secondary pulmonary hypertension.

The etiology and pathogenesis of the vascular lesions characterizing primary pulmonary hypertension (PPH), an often fatal pulmonary vascular disease, are largely unknown. Plexiform lesions composed of proliferating endothelial cells occur in between 20 and 80% of the cases of this irreversible pulmonary vascular disease. Recently, technology to assess monoclonality has allowed the distinction between cellular proliferation present in neoplasms from that in reactive nonneoplastic tissue. To determine whether the endothelial cell proliferation in plexiform lesions in PPH is monoclonal or polyclonal, we assessed the methylation pattern of the human androgen receptor gene by PCR (HUMARA) in proliferated endothelial cells in plexiform lesions from female PPH patients (n = 4) compared with secondary pulmonary hypertension (PH) patients (n = 4). In PPH, 17 of 22 lesions (77%) were monoclonal. However, in secondary PH, all 19 lesions examined were polyclonal. Smooth muscle cell hyperplasia in pulmonary vessels (n = 11) in PPH and secondary PH was polyclonal in all but one of the examined vessels. The monoclonal expansion of endothelial cells provides the first marker that allows the distinction between primary and secondary PH. Our data of a frequent monoclonal endothelial cell proliferation in PPH suggests that a somatic genetic alteration similar to that present in neoplastic processes may be responsible for the pathogenesis of PPH.

Adult↗

Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature.

A case of a 40-year-old man with tuberculous involvement of the epiglottis suffering from unsuspected pulmonary tuberculosis is described. The laryngeal lesions were primarily considered to be highly suspicious for a neoplastic process rather than an infectious one. After diagnosis, the patient was treated according a standard protocol and followed up for a period of 2 years. He is still free of disease. The clinical presentation, diagnosis, pathological findings, and therapy of the condition are described. The differential diagnosis and management of epiglottic tuberculosis are reviewed and discussed. Even though these cases are rare, otorhinolaryngologists should keep in mind the possibility of tuberculosis in the differential diagnosis of laryngeal tumors, as the incidence of tuberculosis in developed countries is steadily increasing.

Adult↗

Nasopharyngeal mass: a manifestation of inflammatory otologic disease.

A nasopharyngeal mass with cranial neuropathies usually indicates an advanced neoplastic process. We present three patients with these findings and concurrent invasive Pseudomonas otitis in whom repeated nasopharyngeal biopsies were negative for tumor. All of the nasopharyngeal masses resolved following treatment of the otitis. Mechanisms of disease spread from the temporal bone to the nasopharynx are discussed. Clinicians may choose to modify diagnostic and therapeutic approaches to the nasopharyngeal mass in patients with concurrent invasive otologic disease.

Aged↗

Tenascin-C is highly expressed in respiratory distress syndrome and bronchopulmonary dysplasia.

Tenascin-C is an extracellular matrix (ECM) glycoprotein expressed in human tissues during organogenesis and in fibrotic and neoplastic processes. We hypothesized that its expression would increase in human lung in neonatal disorders such as infant respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Tenascin-C expression was studied by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH). The extent of tenascin-C immunoreactivity was scored as absent (0), low (+), moderate (++), strong (+++), or very strong (++++) separately in different types of pulmonary cells in controls (seven cases), RDS (19 cases), and BPD (12 cases). In controls, tenascin-C expression was low (+) underneath alveolar and bronchiolar epithelium, moderate (++) in intima of veins, and strong (+++) around chondrocytes. In RDS, tenascin-C expression was moderate (++) or strong (+++) underneath both bronchiolar and often detached alveolar epithelium underlying hyaline membranes in the walls of dilated alveoli. In particular, the patients with RDS who survived for 1 day or more had strong expression of tenascin-C within alveolar walls. In patients with BPD, tenascin-C was very strongly (++++) expressed in the remodeled fibrotic alveolar walls underneath regenerative epithelium. Increased expression of tenascin-C mRNA was seen below the alveolar and bronchiolar epithelia in RDS and BPD. The cells in these locations showed alpha-smooth muscle actin immunoreactivity, suggesting a myofibroblast phenotype. In conclusion, tenascin-C is highly expressed in the walls of alveoli and bronchioli in RDS and BPD, suggesting an association between the expression of this protein and the presence of these disorders.

Actins↗

Morphological studies in a case of thyrotoxicosis complicated by lithium therapy for bipolar depression.

The histological and ultrastructural features of the thyroid in a case of thyrotoxicosis complicated by lithium therapy (for bipolar depression) are described. Despite the bizarre and disturbing pathological appearances, it is proposed that their interpretation should be modified in view of the biosynthetic block imposed by lithium administration. The cellular appearances are considered to reflect a hyperplastic state with coincidental impairment of synthetic activity, and not to represent a neoplastic process. The use of lithium in the management of psychiatric illness is increasing. It is important to be aware of the possible effect of the drug not only on thyroid function but also on the histopathological appearances of the thyroid when interpreting any associated or incidental lesion of the gland.

Adult↗

Trimethobenzamide HCl in the treatment of nausea and vomiting associated with antineoplastic chemotherapy.

Fifty-five patients undergoing chemotherapy for various neoplastic processes were treated with trimethobenzamide or placebo to control nausea and vomiting. Trimethobenzamide was shown to be significantly better than placebo in relieving periodic and total nausea over the 48-hour study. Vomiting incidence was also reduced in the group receiving trimethobenzamide. Differences were noted in the degree of emetic stimulus associated with different chemotherapeutic regimens. No side effects attributable to trimethobenzamide were recorded.

Antineoplastic Agents↗

Evaluation and grading of rat liver foci in carcinogenicity tests.

The significance of rat liver foci in carcinogenesis testing received major attention following their description in the National Cancer Institute workshop of 1974. However, the biological nature of foci remains uncertain despite numerous studies during the past 15 years. That is, in part, because criteria to define foci have been inconsistent, and studies of spontaneous foci in rats have been very few. This symposium has demonstrated that the induction or enhancement of rat liver foci, per se, may not provide sufficient evidence to classify a test compound as a carcinogen. Evidence presented suggests that some types of rat liver foci may not be related to carcinogenesis, and there is, consequently, a basis to further subclassify these lesions. In cases where foci are considered to be a part of the neoplastic process, semi-quantitative grading of these lesions, as well as of tumors, according to the extent of their development or progression, may assist in the interpretation of equivocal carcinogenicity test findings.

Animals↗

Kaposi's sarcoma of the head and neck in patients with acquired immunodeficiency syndrome.

Kaposi's sarcoma is the most common neoplastic process in patients infected with the human immunodeficiency virus. Moreover, the occurrence of Kaposi's sarcoma in human immunodeficiency virus-infected patients advances their classification to having the acquired immunodeficiency syndrome. We reviewed the medical records of 48 patients with human immunodeficiency virus infection who had Kaposi's sarcoma documented on their initial visit to the hospital. The onset of Kaposi's sarcoma occurred independent of the Centers for Disease Control and Prevention classification of human immunodeficiency virus infection (modified to exclude Kaposi's sarcoma). This neoplasm developed more frequently in patients who acquired human immunodeficiency virus infection by sexual contact (75% of cases), but manifestations were not significantly different in any of the risk populations for human immunodeficiency virus infection. Kaposi's sarcoma lesions were unpredictable and either showed progression, remained static, or occasionally, regressed spontaneously. Moreover, the lesions were usually multifocal at presentation, with the head and neck (62.5% of cases) as the primary site of involvement. In this region cutaneous lesions predominated (66.7%), followed by mucosal (56.7%) and deep structure (13.3%) involvement. The majority of patients with acquired immunodeficiency syndrome Kaposi's sarcoma involving head and neck structures were asymptomatic (80% of cases). Mucosal lesions were associated with symptoms in 29.3% of cases, whereas cutaneous lesions had symptoms in 5% of cases.

Acquired Immunodeficiency Syndrome↗

[ Correlation between histopathologic and scintigraphic findings (employing 67Ga) in relation to the surgical indication for bronchial carcinoma (author's transl)].

Following the investigation on the correlation between scintigraphic pictures and histopathologic findings in 66 patients with suspected bronchial carcinoma, 84% of the scannings were positive and the data relative to the so-called "false negative" cases was analyzed. The presence of hilar or mediastinal lymph node metastases, histologically ascertained in about one-third of the patients, appeared significant; and a restricted accumulation of the radio-element was evident in 70.5% of the cases. In 10 of the cases with negative scintigraphic findings, pictures of reactive or hyperplastic lymphadenitis (almost all radiologically relievable) were obtained. Therefore, if it cannot be logically concluded that the negative scintigraphic findings at the mediastinal level indicate the absence of metastases in the lymph nodes, thus indicating surgery (or preventive mediastinoscopy), positive finding seem to be synonymous with extrapulmonary diffusion of the neoplastic process, with direct implication in determining the operability of the patient.

Bronchial Neoplasms↗

Age characteristics of mesothelioma incidence in the general population of the province of Padova, 1965-1976.

Twenty-four incidental cases of mesothelioma, diagnosed in the province of Padova during the period 1965-1976, were analyzed according to age characteristics. The results show that the incidence rate increases in the general population under study at the same rate as in other populations occupationally and non-occupationally exposed to carcinogenic fibers according to the time since first exposure. This finding suggests a similar neoplastic process independent of age, in different environmental situations.

Adult↗

Cancer of the appendix in long-standing ulcerative colitis: a case report.

Cancer of the appendix was found in a 69-year-old female patient affected by long-standing ulcerative colitis (UC). On histological examination the cancer was a typical cystadenocarcinoma of the appendix. The appendiceal mucosa not invaded by the neoplastic process was normal. Histological examination of the colorectal mucosa did not show dysplasia or cancer. These findings suggest that appendiceal cancer and UC may be unrelated diseases. A surveillance program for early detection of cancer of the appendix in patients with long-standing UC does not seem mandatory.

Aged↗

Keratinocytes and cytokine/growth factors.

Cytokines are polypeptide growth factors produced by most nucleated cells in the body, including epithelial cells, keratinocytes, and Langerhans cells in the skin. Cytokines can be classified into interleukins, tumor necrosis factors, chemokines, colony-stimulating factor, interferons, and growth factors. Like classic hormones, cytokines bind to specific receptors to transmit their messages to target cells. Cytokine receptors can be divided into three cytokine receptor superfamilies: the immunoglobulin superfamily, the hematopoietin family, and the tumor necrosis factor family. Following cytokine/cytokine-receptor binding (first messenger), a signal transduction pathway is initiated. Factors affecting homeostasis in the skin and oral mucosa include a delicate balance between cytokines/cytokine-receptors and their antagonists. An imbalance in these variables can influence the development of cutaneous and oral diseases-such as lichen planus, autoimmune disorders, and some neoplastic processes- and can affect wound healing. Potential uses of cytokines include cancer and antiviral therapy.

Chemokines↗