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PubMed1993

A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility. II. Exposure assessment.

A case-control study of malignant and non-malignant respiratory disease among employees of the Owens-Corning Fiberglas Corporation's Newark, Ohio plant was undertaken. The aim was to determine the extent to which exposures to substances in the Newark plant environment, to non-workplace factors, or to a combination may play a part in the risk of mortality from respiratory disease among workers in this plant. A historical environmental reconstruction of the plant was undertaken to characterise the exposure profile for workers in this plant from its beginnings in 1934 to the end of 1987. The exposure profile provided estimates of cumulative exposure to respirable fibres, fine fibres, asbestos, talc, formaldehyde, silica, and asphalt fumes. Employment histories from Owens-Corning Fiberglas provided information on employment characteristics (duration of employment, year of hire, age at first hire) and an interview survey obtained information on demographic characteristics (birthdate, race, education, marital state, parent's ethnic background, and place of birth), lifetime residence, occupational and smoking histories, hobbies, and personal and family medical history. Matched, unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and the cumulative exposure history, demographic characteristics, and employment variables. Only the smoking variables and employment characteristics (year of hire and age at first hire) were statistically significant for lung cancer. For non-malignant respiratory disease, only the smoking variables were statistically significant in the univariate analysis. Of the variables entered into a conditional logistic regression model for lung cancer, only smoking (smoked for six months or more v never smoked: OR = 26.17, 95% confidence interval (95% CI) 3.316-206.5) and age at first hire (35 and over v less than 35: OR = 0.244, 95% CI 0.083-0.717) were statistically significant. There were, however, increased ORs for year of employment (first hired before 1945 v first hire after 1945: OR = 1.944, 95% CI 0.850-4.445), talc (cumulative exposure >1000 fibres/ml days v never exposed: OR = 1.355, 95% CI 0.407-5.515), and asphalt fumes (cumulative exposure >0.01 mg/m(3) days v never exposed: OR 1.131, 95% CI 0.468-2.730). For non-malignant respiratory disease, only the smoking variable was significant in the conditional logistic regression analysis (OR = 2.637, 95% CI 1.146-6.069). There were raised ORs for the higher cumulative exposure categories for respirable fibres, asbestos, silica, and asphalt fumes. For both silica and asphalt fumes, ORs were more than double the reference groups for all exposure categories. A limited number of subjects were exposed to fine fibres. The scarcity of cases and controls limits the extent to which analyses for fine fibre may be carried out. Within those limitations, among those who had worked with fine fibre, the unadjusted, unmatched OR for lung cancer was (1.0 (95% CI 0.229-4.373) and for non-malignant respiratory disease, the OR was 1.5 (95% CI 0.336-6.702). The unadjusted OR for lung cancer for exposure to fine fibre was consistent with that for all respirable fibre and does not suggest an association. For non-malignant respiratory disease, the unadjusted OR for fine fibre was opposite in direction from that for all respirable fibres. Within the limitations of the available data on fibre, there is o suggestion that exposure to fine fibre has resulted in an increase in risk of lung cancer. The increased OR for non-malignant respiratory disease is inconclusive. The results of this population, in this place and time, neither respirable fibres nor any of the substances investigated as part of the plant environment are statistically significant factors for lung cancer risk although there are increased ORs for exposure to talc and asphalt fumes. Smoking is the most important factors in risk for lung cancer in this population. The situation is less clear for non-malignant respiratory disease. Unlike lung cancer, non-malignant respiratory represents a constellation of outcomes and not a single well defined end point. Although smoking was the only statistically significant factor for non-malignant respiratory disease in this analysis, the ORs for respirable fibres, asbestos, silica, and asphalt fumes were greater than unity for the highest exposure categories. Although the raised ORs for these substances may represent the results of a random process, they may be suggestive of an increased risk and require further investigation.

Adult↗

PubMed2006

Distinguishing benign from malignant pulmonary nodules with helical chest CT in children with malignant solid tumors.

PURPOSE: To retrospectively assess whether computed tomographic (CT) findings can indicate the benign or malignant nature of pulmonary nodules in pediatric patients with malignant solid primary tumors. MATERIALS AND METHODS: With institutional review board approval, waived parental and patient consent, and HIPAA compliance, the authors determined the incidence of malignancy among 81 pulmonary nodules that were sampled at biopsy within 3 weeks after chest CT (January 1999 to September 2003) in 41 young patients with malignant solid tumors. Three radiologists independently and retrospectively reviewed these scans and the available previously obtained scans, classifying nodules as benign, malignant, or indeterminate on the basis of their number, unilateral versus bilateral distribution, size, margins (indistinct vs distinct), calcification, growth, and associated adenopathy. These classifications were compared with nodule histologic type, and interreviewer agreement was assessed. RESULTS: The median patient age was 14.8 years (mean, 13.7 years; range, 5-21 years). Twenty-four of the 41 patients (58%) had at least one biopsy-proved malignant nodule. Four (10%) patients had both benign and malignant nodules; 17 (42%) had only benign nodules. Reviewer 1 classified 65% (39 of 60) of nodules correctly; reviewer 2, 57% (37 of 65); and reviewer 3, 67% (43 of 64). Interreviewer agreement was slight to moderate (kappa </= 0.43, P </= .03). In contrast to findings in adults, sharply defined nodules in younger individuals were more likely to be malignant (P = .03) and nodule size was not associated with malignancy (P >/= .32). CONCLUSION: The frequency of benign nodules and the inconsistency of predictions based on CT features suggest the need for better predictors of pulmonary nodules being malignant or benign, so as to reduce unnecessary thoracotomy in pediatric patients with solid malignancy. .

Adolescent↗

PubMed2003

Malignant and non-malignant asbestos-related pleural and lung disease: 10-year follow-up study.

AIM: To examine the presence of radiologically visible lung and pleural changes in patients who were exposed to the asbestos dust, and to correlate the progression of these changes with the duration and intensity of exposure and smoking. We also evaluated possible correlation between non-malignant asbestos-related pleural abnormalities and the occurrence of malignant pleural mesothelioma. METHODS: Among 7,300 patients who visited our department between 1991 and 2000 due to non-specific respiratory symptoms, we selected 2,420 with chest X-rays indicating the possible existence of non-malignant asbestos-related diseases. The selected group was followed-up for progression of radiological changes and the development of malignant pleural mesothelioma, and the changes were correlated with the intensity and duration of exposure to asbestos dust and smoking. RESULTS: Radiological changes characteristic for non-malignant asbestos-related pleural disease or lung asbestosis were identified in 340 (14%) out of 2,420 examined patients, of whom 77 (22.6%) developed malignant pleural mesothelioma, as compared with 13 patients out of 2,080 (0.6%) without radiological signs of asbestosis or pleural changes. Twenty-three (29.9%) patients who presented with a progression of pleural disease and lung asbestosis had a very significant incidence of malignant pleural mesothelioma (p<0.001). We also found that 55 (71.4%) patients with the highest asbestos exposure level (grade 3) developed malignant pleural mesothelioma more often (p=0.044). No correlation was found between malignant pleural mesothelioma development and duration of asbestos exposure (p=0.149) or smoking habit (p=0.617). Professionally exposed patients were at 3.3-times higher relative risk (95% confidence interval, 2.28-4.75) than those who were not exposed to develop malignant pleural mesothelioma. CONCLUSIONS: The risk of developing lung asbestosis increased with the level of exposure to asbestos dust and smoking. The risk of developing pleural disease correlated with the intensity and duration of exposure, but not with smoking. The patients with progressive pleural and parenchymal changes are at particularly high risk of developing malignant pleural mesothelioma and must be under special surveillance.

Adolescent↗

PubMed1993

Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy.

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2004

Expression of cytokeratin by malignant meningiomas: diagnostic pitfall of cytokeratin to separate malignant meningiomas from metastatic carcinoma.

Based on clinical and histologic features, differentiating metastatic carcinomas from benign or malignant meningiomas usually is not difficult. Occasionally, however, in some patients without a clinical history of carcinoma, malignant meningiomas can morphologically simulate metastatic carcinoma, necessitating an immunohistochemical study for cytokeratin to make a correct diagnosis. However, the utility of immunohistochemical markers to separate malignant meningioma from metastatic carcinoma has not been investigated. The immunoperoxidase method with antigen retrieval was used to characterize the expression of three cytokeratins (AE1/AE3, CAM 5.2, and Pan cytokeratin), EMA, CEA, Ber-EP4, CD 15, and B72.3 in 12 previously diagnosed malignant meningiomas, 20 benign meningiomas, and 20 metastatic carcinomas. Cytokeratin expression was detected in 75% of malignant meningiomas, 0% of benign meningiomas, and 100% of metastatic carcinomas. While epithelial markers of Ber-EP4, CEA, B72.3 and CD-15 were positive in 90, 80, 70 and 65% of the metastatic carcinoma, respectively, they were negative in all 12 malignant meningioma examined. Vimentin immunoreactivity was seen in all benign and malignant meningiomas, and in 20% of metastatic carcinomas. Our results indicated that cytokeratin is not a reliable immunohistochemical marker to separate a malignant meningioma from metastatic carcinoma. A panel of epithelial markers including Ber-EP4, CEA, B72.3 and CD-15, and vimentin may be needed to separate malignant meningioma from metastatic carcinoma. Cytokeratin expression can be a potential pitfall for confusing a malignant meningioma with a metastatic carcinoma.

Antibodies, Neoplasm↗

PubMed2003

The expression of somatostatin receptors 1 and 2 in benign, pre-malignant and malignant laryngeal lesions.

The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane-bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre-malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre-malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low-to-moderate levels in only 2/6 (33%) pre-malignant and 3/12 (25%) malignant specimens (P < 0.01). This 'loss' of epithelial SSTR2 expression may provide a growth advantage in pre-malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre-malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.

Adult↗

PubMed2006

The association between malignant melanoma and noncutaneous malignancies.

BACKGROUND: Both increases and decreases in the incidence of subsequent malignancies in melanoma patients have been reported. We examined the database of the Indiana University Cancer Center to determine whether there is an association between malignant melanoma and noncutaneous malignancies. OBJECTIVE: We searched for evidence of noncutaneous malignancies in a cohort of melanoma patients. METHODS: Patients with microscopically confirmed malignant melanoma diagnosed between January 1987 and March 2001 were analyzed. This cohort was investigated for noncutaneous malignancies occurring either before or after the diagnosis of melanoma. The standardized incidence ratios (SIR) were calculated as the ratio of the observed to the expected number of patients with second malignancies, and 95% confidence intervals (95% CI) around the SIR were estimated from the cumulative Poisson distribution. RESULTS: A total of 955 patients with melanoma (498 males and 457 females) were documented over the 14-year period. Sixty-nine noncutaneous malignancies were identified in 59 (6.2%) melanoma patients (39 males and 20 females). There was a higher risk of non-Hodgkin's lymphoma (SIR = 1.91; 95% CI, 0.88-3.62) in men and renal cell carcinoma (SIR = 2.41, 95% CI, 0.97-4.97) in men. In female patients, however, there was no higher risk of noncutaneous malignancies. CONCLUSIONS: This study did not show a higher risk of prostate cancer, gastrointestinal cancer, leukemia, endometrial cancer, or cancer of the nerve and neuroendocrine systems in melanoma patients. No female patients incurred a higher risk of noncutaneous cancers. The increased risk of non-Hodgkin's lymphoma and renal cell carcinoma in men might be attributed to a mutual carcinogenic exposure, an aberration of cell-mediated immunity, a shared genetic susceptibility, increased medical surveillance among cancer patients, a post-therapy effect after cancer management, or factors not as yet clear. Close monitoring of melanoma patients for signs of second malignancy is warranted.

Carcinoma, Renal Cell↗

PubMed1999

Malignant melanoma arising from nevi, p53, p16, and Bcl-2: expression in benign versus malignant components.

BACKGROUND: The etiology of malignant melanoma has been the subject of much study. Tumour suppressor genes p53 and p16 and the antiapoptotic, Bcl-2, are implicated in the development and progression of malignant melanoma. OBJECTIVE: To compare the expression of p53, p16, and the Bcl-2 genes in both benign and malignant components of malignant melanoma arising from pre-existing nevocellular nevi. METHODS: Twenty cases of malignant melanoma arising from pre-existing nevi were selected and studied by immunohistochemistry for the expression of p53 (D07) CDK4I/MTS-1/INK <4, which detects both wild and mutant type, p16 CDK4I/MTS-1/INK <4, and Bcl-2 using an avidin-biotin technique on formalin-fixed, paraffin-embedded sections. RESULTS: Fifteen cases demonstrated p53 immunoreactivity in the malignant components ranging from 5 to 20% with no expression being seen in the benign components. The p16 gene showed strong nuclear reactivity in the benign components of 14 cases and weak reaction in 6 cases; the malignant components expressed weak nuclear staining in 18 cases and cytoplasmic staining in all cases. The Bcl-2 gene was expressed strongly to moderately in benign components and weakly in malignant components of nine cases, and was negative in 11 cases. CONCLUSION: Immunostaining for p53 is expressed only in the malignant component, whereas p16 and Bcl-2 showed decreased staining and a different pattern in malignant compared with benign components. These findings suggest that expression and alterations in the subcellular localization of the cell cycle regulators may contribute to the mechanism of tumourigenesis.

Cell Transformation, Neoplastic↗

PubMed2006

Predictive value of breast lesions of "uncertain malignant potential" and "suspicious for malignancy" determined by needle core biopsy.

BACKGROUND: The optimum management of patients whose needle core biopsy (NCB) results are of "uncertain malignant potential" (B3) or "suspicious for malignancy" (B4) is unclear. This study correlates B3 and B4 NCB findings with excision histology to determine associated rates of malignancy. METHODS: All NCBs categorized as B3 or B4 were identified from a series of 3729 NCBs. Results of biopsies were reported as normal/nondiagnostic (B1), benign (B2), uncertain malignant potential (B3), suspicious but not diagnostic of malignancy (B4), or malignant (B5) according to the B classification system. B3 lesions included atypical intraductal epithelial proliferations (AIEPs), lobular neoplasia, papillary lesions, radial scars, and potential phyllodes tumors. Histological concordance between NCB and excision specimen was analyzed. RESULTS: A total of 211 B3 lesions and 51 B4 lesions were identified during the study period. The open biopsy rate after a B3/B4 finding was 86% (n = 226). The overall rate of malignancy for B3 lesions after excision was 21%. The B3 lesion-specific rates of malignancy were 6% for radial scars, 14% for papillomas, 35% for AIEP, and 44% for lobular neoplasia. Of the patients with a B4 categorization, 90% (44 of 49) were diagnosed with carcinoma after surgery. Those that were "suspicious for ductal carcinoma-in-situ" and "suspicious for invasion" correlated accurately with excision findings in 81% and 89% of patients, respectively. CONCLUSIONS: Management of lesions in the B3 categorization must be tailored to the patient because the specific lesion types are associated with highly variable rates of malignancy. A repeat biopsy or a therapeutic wide local excision should be undertaken in lesions with a B4 NCB categorization because such lesions are associated with a particularly high risk of malignancy at excision.

Biopsy, Needle↗

PubMedDate not supplied

Attachment, spreading and growth in vitro of highly malignant and low malignant murine fibrosarcoma cells.

Highly malignant cell lines and low-malignant cell lines isolated from three different methylcholanthrene-induced murine fibrosarcomas were examined for their ability to attach to plastic dishes and collagen-coated dishes under serum-free conditions and in the presence of serum. Most of the cells from the three highly malignant lines attached and spread under all conditions. By 72 h, there was a significant increase in the number of cells indicating that at least some of the cells had undergone division (even in the absence of serum). In contrast, fewer of the cells from the three low-malignant lines attached and spread on the plastic or collagen substrates in the absence of serum or in the presence of 0.1 per cent serum. However, when 15 micrograms laminin per dish was added along with the low-malignant cells, they then attached and spread on the plastic and collagen-coated dishes. Previous studies have indicated that the highly malignant lines express cell surface antigens that cross-react with laminin while the low-malignant cell lines do not. We speculate that the differences between the high- and low-malignant cells in the expression of cell surface laminin-like antigens contribute to the dissimilarities in attachment and spreading capacity. These differences may also contribute to the dissimilarity between these cells in malignant potential.

Animals↗

PubMed2003

[Pre-malignant and malignant lesions in minor surgery at a health centre. Appearances can't be trusted].

OBJECTIVE: To describe the characteristics of the malignant and pre-malignant lesions found in the minor surgical interventions performed at a health centre. DESIGN: Retrospective, descriptive study. PARTICIPANTS: 682 lesions: all the lesions extirpated and referred to pathology except for epidermal and trichilemmal cysts, lipomas, molluscum, common warts, and nails. SETTING: Rochapea Health Centre, Pamplona.Main measurements. We analysed the anatomical-pathological results and the distribution by sex, age-group, location, technique and edges affected in 27 dysplasias and 11 malignant lesions. RESULTS: We found that malignant and pre-malignant lesions were more common in women, aged 15 to 44 for dysplasias and 45-64 for malignant lesions. The most common location was on the back; the most frequent technique, fusiform excision. This technique had the highest percentage of edges without lesion in dysplasias. The lesions whose edges were affected corresponded to punch and circular excision samples. None of the malignant lesions had their edges affected. CONCLUSIONS: Most malignant lesions are not suspected. They appear in samples referred with a diagnosis of benign. Employment of techniques such as fusiform excision in lesions which are potentially malign, even though in principle they seem benign, enables them to be extirpated with free edges.

Adolescent↗

PubMed2001

Malignant mixed tumor ex eccrine spiradenoma: an unusual pattern of malignant dedifferentiation.

Eccrine spiradenoma (ES) is a benign tumor of the skin adnexal origin. It is often seen in the head and neck region of young adults and may be present for years. While there have been numerous case reports of malignant degeneration within ES, they have been mostly carcinomatous dedifferentiation and rarely carcinosarcomas. A malignant mixed tumor is a neoplasm with a malignant epithelial component and areas of chondroid and myxoid differentiation within the malignant epithelial proliferation. While the epithelial component is malignant, the mesenchymal component is felt to represent a benign, metaplastic response of the stroma. While the malignant mixed tumor has a benign counterpart, the benign mixed tumor, the former is usually not seen in continuity with the latter. We describe a case of ES with malignant degeneration and demonstrate the transformation from benign to malignant. The histology and immunohistochemistry of the neoplasm supports a malignant mixed tumor, an extremely unusual neoplasm to see in association with ES or any benign adnexal neoplasm.

Adenoma, Sweat Gland↗

PubMed1996

Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation.

BACKGROUND: Malignancy is generally considered a contraindication for cardiac transplantation, whereas secondary malignancy has been described under chronic immunosuppression. PATIENTS AND METHODS: We report here the frequency of malignancy encountered among the 495 patients evaluated at our cardiac transplant centre as well as the incidence and the course of post-transplant malignancy among 129 consecutive patients who underwent cardiac-transplantation, with a subsequent minimum follow-up of 6 months. RESULTS: A total of 10 out of 495 patients (2%) evaluated for heart transplantation presented with a history of previous malignancy: 3 of them underwent transplantation (2 survive, 1 died) whereas in the remaining 7 patients neoplasia was considered a contraindication for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths). Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 +/- 15 months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3 solid tumors). No significant association was found between post-transplant malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine antihuman T-cell monoclonal antibodies (OKT3). CONCLUSION: These results confirm that pre-transplant malignancy is not an absolute contraindication for cardiac transplantation and that post-transplant follow-up must include careful monitoring of post-transplant malignancy.

Adolescent↗

PubMed2003

[A case of triple malignancies (gastric cancer, lung cancer and malignant pleural mesothelioma) after asbestos exposure].

This case study centers on a seventy-eight-year-old man with triple malignancies, namely, gastric cancer, lung cancer and malignant pleural mesothelioma, all of which developed at different times. The histological types were adenocarcinoma of the stomach, squamous cell carcinoma of the lung and sarcomatous malignant pleural mesothelioma. Gastric cancer was treated by endoscopic mucosal resection 2 years ago. The patient presented with a chief complaint of dyspnea, and right pleural effusion was found on chest radiography. The right-side effusion disappeared spontaneously, but a small mass on the left side was diagnosed as lung cancer, and so left inferior lobe resection was performed. Malignant pleural mesothelioma appeared after one year of pleural effusion and the patient died of mesothelioma one year after diagnosis. At autopsy, the gastric cancer and lung cancer had not relapsed and malignant pleural mesothelioma had metastasized to the lung, liver, adrenal gland and small intestine. He was a sailor by profession and it was obvious that he had been exposed to asbestos, because 538 asbestos bodies per 5 g of wet lung tissue were detected. His advanced age was one of the risk factors for the multiple malignancies, and the asbestos exposure was considered to have compounded these hazards to cause the triple malignancies. It is well known that lung cancer and malignant mesothelioma are induced by asbestos exposure, but multiple cancers including lung cancer and malignant mesothelioma are extremely rare.

Adenocarcinoma↗

PubMed2003

The impact of progesterone on simultaneous, local secretion of IGFBP-3 and IGF-I [IGFBP-3/IGF-I index] by human malignant and non-malignant breast explants depends on tissue steroid receptor phenotype.

OBJECTIVES: Insulin-like growth factor-I (IGF-I) is regarded as one of mammary tissue proliferative factors. Insulin-like growth factor binding protein-3 (IGFBP-3) limits the IGF-I binding potential to its receptor. That limits the IGF-I bioavailability. Recently experimental studies indicated that insulin-like growth factor binding proteins (IGFBPs) might have their own biological actions beyond their ability to regulate insulin-like growth factors (IGFs). Our earlier results showed the progesterone-induced rise in hGH and IGF secretion by human breast cancer explants. AIM: To determine the ability of progesterone to stimulate simultaneous local IGF-I and IGFBP-3 secretion by non-malignant and malignant mammary tissue collected from different receptor phenotype tumours. MATERIAL AND METHODS: Explants from the tumour and surrounding normal non-malignant tissue were obtained during surging. Breast cancer explants were defined as: ER+ PR+; ER-PR-; ER+ PR-; and ER-PR+. Part of the explants was fixed in 10% buffered formalin for steroid receptor determination by immunohistochemistry. Other parts were cut into small pieces, weight and cultured in Parker medium (M199) supplemented with 5% of calf serum at 37 degrees C in an atmosphere containing 5% CO2 for 48 hours in control medium or with the addition of progesterone (10-7 M). Later media were collected for IGF-I and IGFBP-3 concentration analysis. RESULTS: Progesterone increased (p < 0.01) IGFBP-3/IGF-I index in ER(-)PR(-) non-malignant tissue and decreased the IGFBP-3/IGF-I index in ER(-)PR(+), ER(+)PR(-) non-malignant explants. That increased the IGF-I bioavailability. Breast malignant explants showed the progesterone induced IGFBP-3/IGF-I index decrease. The decrease was most evident (p < 0.01) in malignant explants expressing progesterone receptor. CONCLUSION: Progesterone increased local IGF-I bioavailability in malignant breast tissue. That phenomenon depended on steroid receptor phenotype of breast tissue and was most evident in tissue expressing progesterone receptor. In non-malignant tissue that phenomenon was also found in estrogen receptor expressing tissue. Lack of steroid receptor expression in breast explants reversed that phenomenon.

Biomarkers, Tumor↗

PubMedDate not supplied

Is neuroleptic malignant syndrome a neurogenic form of malignant hyperthermia?

Neuroleptic malignant syndrome is a rare and potentially lethal disorder associated with the use of antipsychotic medications. Heightened vigilance on the part of clinical providers has reduced morbidity and mortality caused by this disorder over the past decade, but there is still no consensus regarding its diagnosis, pathophysiology, or treatment. Efforts to demonstrate a direct link between neuroleptic malignant syndrome and malignant hyperthermia have been unsuccessful, indicating mutually distinct etiologies despite striking clinical similarities. This paper concisely reviews essential aspects of electromechanical transduction in muscle and nerve cells and current knowledge concerning the pathophysiology of malignant hyperthermia and neuroleptic malignant syndrome. Utilizing this conceptual framework, the author proposes that neuroleptic malignant syndrome may be caused by a spectrum of inherited defects in genes that are responsible for a variety of calcium regulatory proteins within sympathetic neurons or the higher order assemblies that regulate them. In this proposed model, neuroleptic malignant syndrome may be understood as a neurogenic form of malignant hyperthermia.

Animals↗

PubMed1987

Comparative studies of human malignant mesothelioma in vivo, in xenografts in nude mice, and in vitro. Cell origin of malignant mesothelioma.

Several decades ago, it was reported that normal and malignant mesothelial cells were transformed into distinct cell types (epithelial to fibrous and fibrous to epithelial) when transferred to in vitro conditions. Those tissue culture data are still cited as evidence supporting that the mesothelial cell has multipotentiality of differentiation and the mesothelial cell is a sole precursor of malignant mesothelioma cells. Six cell lines of heterotransplanted human malignant mesothelioma in nude mice and one cell line of subcultured human malignant mesothelioma in vitro have been established. To establish the validity of the classic concept of multipotentiality of malignant mesothelioma, we studied malignant mesothelioma cells of the seven cases using in vivo cultures, xenografts in nude mice and an in vitro tissue culture, utilizing histology, histochemistry, immunocytochemistry and electron microscopy. The nature of the original malignant mesothelioma cells was clearly shown to be well preserved in both the heterotransplanted and subcultured cells. Data did not support earlier hypotheses that mesothelial cells are capable of differentiating into distinct cell lines. The mesothelial cell and the submesothelial connective tissue cells are the precursors of the neoplastic cells in malignant mesothelioma.

Aged↗

PubMed1985

Proteinase-like peptidase activities in malignant and non-malignant gastric tissue.

Activities of several proteinase-like peptidases have been determined in homogenates of malignant tissue, non-malignant tissue adjacent to the tumour (A-NM) and non-malignant tissue distant to the tumour (D-NM) from 17 patients undergoing surgery for histologically confirmed gastric malignancies. In homogenates of malignant tissues the activities of collagenase, cathepsin B, cathepsin (B+L), cathepsin H and cathepsin D were significantly higher than in D-NM tissues. By contrast, the levels of plasminogen activator were significantly lower in malignant tissues than in the D-NM tissues. Furthermore, the activities of collagenase-like and the cysteine-proteinase-like peptidases in the A-NM tissues were lower than in malignant tissues but higher than in the D-NM tissues. Separation of full-thickness non-malignant tissues into mucosal and seromuscular layers revealed significantly higher activities in the former. The elevated levels of these proteinase-like peptidases in homogenates of gastric cancer tissue suggests an important role for these enzymes in tumour invasion.

Aged↗