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PubMed1989

An autopsy study of lung cancer with special reference to the relationship between cigarette smoking and histological differentiation of adenocarcinoma and squamous cell carcinoma.

To clarify the relationship between cigarette smoking and the degree of differentiation of adenocarcinoma and squamous cell carcinoma of the lung, 207 male and 103 female cases of adenocarcinoma and 125 male and 26 female cases of squamous cell carcinoma, autopsied between 1958 and 1985, were reviewed. In males, adenocarcinoma cases increased as the degree of differentiation decreased. In females, poorly differentiated cases of adenocarcinoma and, in males, those of squamous cell carcinoma, were minimal, and the number of poorly-differentiated adenocarcinoma cases significantly less (p less than 0.005) in females than in males. The number of male smokers with adenocarcinoma increased, and that of female non-smokers decreased, as the degree of differentiation decreased. On the other hand, the number of male smokers with squamous cell carcinoma decreased and that of female non-smokers increased as the degree of differentiation decreased. The incidences of well-differentiated adenocarcinoma in female non-smokers, well-differentiated squamous cell carcinoma in male heavy smokers and poorly-differentiated squamous cell carcinoma in female non-smokers were prominent. A histopathological diagnoses of differentiated subtypes of adenocarcinoma and squamous cell carcinoma of the lung is useful and important in understanding the biological characteristics of lung cancer and also the effects of cigarette smoking.

Adenocarcinoma↗

PubMed1989

[Studies on antigen associated with human squamous cell carcinoma (SCC antigen) in patients with esophageal carcinoma].

The authors studied on SCC antigen in patients with esophageal carcinoma. Serum SCC antigen was found in 9 (40.9%) of 22 patients with esophageal squamous cell carcinoma and 5 (55.5%) of 9 patients with lung squamous cell carcinoma, but was not found in other malignant diseases, such as gastric cancer, hepatoma, colon cancer, pancreas cancer and biliary try tract cancer. SCC antigen positive cases increased in association with progression of histological invasion, grade of nodal metastasis and clinical stage. However, in early esophageal carcinoma, SCC antigen was rarely positive. There was no positive case in patients with poorly differentiated squamous cell carcinoma regardless of clinical stage. Positive rate of SCC antigen increased in association with progression of clinical stage in patients with moderately and well differentiated squamous cell carcinoma. Immunoreactivity of SCC, which was investigated immunohistologically with TA-4 rabbit serum, was not found in cases with poorly differentiated squamous cell carcinoma, but was found in keratinized portion and cytoplasm of moderately and well differentiated carcinoma. From the above, SCC antigen is intimately related with keratinization of squamous cell carcinoma, and it was thought that it could be useful as a good marker for diagnosis of moderately and well differentiated squamous carcinoma of the esophagus.

Antigens, Neoplasm↗

PubMed1989

Squamous carcinoma of the esophagus in patients with Barrett esophagus.

Adenocarcinoma of the esophagus is a well-known complication of Barrett esophagus, especially in white men. We present three cases of squamous carcinoma of the esophagus in Barrett patients. All three patients were white men. None had a history of symptomatic gastroesophageal reflux or of Barrett esophagus, but all had substantial usage of alcoholic beverages and tobacco. All three tumors were located in squamous-lined mucosa above the Barrett mucosa. Columnar epithelial dysplasia was present in the Barrett mucosa of two of our patients, and the third patient had a squamous carcinoma of the pharynx. Squamous carcinoma represented 2% of Barrett-associated esophageal carcinomas at our institution in 1980 through 1986. Five additional cases were found in the literature, and all were also in white men. This demographic predominance stood in striking contrast to the 26% prevalence of white patients among those with squamous carcinoma of the esophagus at our institution (P less than 0.0002) and to the 50% prevalence of white men among our patients with Barrett esophagus (P less than 0.02). Two of the literature cases also had substantial alcohol and tobacco usage and had synchronous adenocarcinoma arising in Barrett mucosa. Our findings of a strikingly high prevalence of white men and of multifocal neoplastic changes in the upper aerodigestive tract suggest a pathogenetic relationship between squamous carcinoma of the esophagus and Barrett esophagus, possibly due to alcoholic beverage and tobacco usage. Endoscopic surveillance of Barrett patients for early detection of adenocarcinoma has been recommended; contemporaneous evaluation of the squamous-lined esophagus by biopsy and cytopathology may be advisable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1984

Profiles of keratin proteins in basal and squamous cell carcinomas of the skin. An immunohistochemical study.

Profiles of immunohistochemical staining for different molecular weight keratin proteins (45, 46, 55, and 63 kilodalton (kd] were evaluated in basal and squamous cell carcinomas of the skin and surrounding epidermis. Basal cell carcinomas predominantly stained with antisera to low molecular weight keratins (45 and 46 kd). Staining with antisera to higher molecular weight keratins (55 and 63 kd) was focal and restricted to areas of squamous differentiation. Invasive squamous cell carcinomas in addition to staining with antisera to low molecular weight keratins (45 and 46 kd) showed diffuse staining for 55-kd keratin and foci of staining for 63-kd keratin most prominent in keratinized regions of the tumors. In situ squamous cell carcinomas (Bowen's disease) differed from invasive squamous cell carcinoma in showing increased staining for high molecular weight keratin (63 kd). Abnormal keratin profiles were identified adjacent to and overlying basal and squamous cell carcinomas, with antisera to low molecular weight keratins (45 and 46 kd) staining all layers of the epidermis, and decreased intensity of staining for high molecular weight keratin (63 kd). Keratin profiles may help define abnormal squamous maturation in epidermis adjacent to tumors. Immunohistochemical staining for different molecular weight keratin proteins may also be helpful in the differential diagnosis of skin lesions.

Basal Cell Carcinoma↗

PubMed1982

Squamous cell carcinoma arising from an epidermoid cyst in the ovary of a rat treated with 7,12-dimethylbenz[a]anthracene.

Primary non-teratomatous ovarian squamous cell carcinomas are very rare. A case of rat ovarian squamous cell carcinoma has been found in which the tumor arose from a squamous element in the ovary. Squamous epithelial aggregates were found in the wall of a cyst and on serial section, the cyst was found to be unaccompanied by any teratomatous components and showed a thin squamous epithelial lining with keratinizing debris. On the basis of these findings, it was suggested that the squamous element was a rat ovarian epidermoid cyst from which a squamous cell carcinoma arose, presumably by a direct carcinogenic effect of 7,12-dimethylbenz[a]anthracene.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Serum CYFRA 21-1 assay in squamous cell carcinoma of the cervix.

Squamous cell carcinoma antigen (SCC) is the best known marker for squamous cell carcinoma of the cervix as well as of the lung, oesophagus, head and neck and anal canal. Elevated levels of cytokeratin 19-fragments (CYFRA 21-1) have recently been detected in a large proportion of patients with non small cell cancer of the lung, and in particular of those with squamous cell carcinoma. Serum levels of CYFRA 21-1 (cut-off = 1.06 ng/mL) and SCC (cut-off = 2 ng/mL) were measured in blood samples collected before treatment from 15 patients with cervical intraepithelial neoplasia (CIN), 56 patients with cervical cancer, 48 patients with endometrial cancer, and 361 patients with benign uterine diseases. Serum CYFRA 21-1 values in patients with CIN were superimposable on those detected in patients with benign uterine diseases. Conversely, serum CYFRA 21-1 levels were higher in patients with cervical cancer (p < 0.05) and in patients with endometrial cancer (p < 0.05) than in those with benign uterine diseases. There was no significant difference in serum CYFRA 21-1 levels between cervical and endometrial cancer, and, as regards cervical cancer, there was no significant difference in antigen values between squamous cell carcinoma and adenocarcinoma. Among patients with squamous cell carcinoma of the cervix, CYFRA 21-1 values correlated with FIGO stage (stage IIb-IV vs stage Ib-IIa, p = 0.0303). Elevated CYFRA 21-1 levels were found in 20.0% of patients with CIN, in 41.7% of patients with squamous cell carcinoma of the cervix, in 62.5% of patients with adenocarcinoma of the cervix, in 45.8% of patients with endometrial cancer, and in 13% of patients with benign uterine diseases. Serum SCC was more sensitive than serum CYFRA 21-1 for both early and advanced squamous cell carcinoma of the cervix; these preliminary data seem to show that serum CYFRA 21-1 is of limited value for the management of patients with this malignancy.

Adenocarcinoma↗

PubMed1995

Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas.

UNLABELLED: BACKGROUND/DESIGN: The clonal theory of cancer predicts that transformed cells within a given tumor are derived from a single initiated precursor. Advancement of this precursor through various stages of tumor development occurs with the further accumulation of selective genetic and epigenetic lesions. Mammalian ras genes are important constituents of mitogenic signaling pathways, and when activated, they contribute to deregulated cellular growth. Activated ras genes play important roles in the development of certain skin tumors. Studies on a number of animal tumor model systems have shown that ras gene activation can be an early and perhaps initial event in the development of skin tumors. Activated ras genes are also found in a significant percentage of somatic human squamous cell carcinomas. To gain retrospective insight into the stages at which activated ras genes contribute to squamous cell carcinoma development, we investigated their incidence in actinic keratoses, premalignant precursors to squamous cell carcinomas. Using a nonradioactive polymerase chain reaction-based method developed in our laboratory, we examined a panel of 19 actinic keratoses and 33 squamous cell carcinomas for activated ras genes. RESULTS: DNA analysis revealed ras gene mutations in three (16%) of 19 actinic keratoses and in four (12%) of 33 squamous cell carcinomas. Activating mutations occurred at codon 12 of the K-ras gene, and codons 12, 13, and 61 of the H-ras gene. All positive actinic keratoses and squamous cell carcinomas occurred in sun-exposed regions. CONCLUSIONS: Activated ras genes can play important roles during early stages of squamous cell carcinoma development. Aberrant repair of UV-induced pyrimidine dimers is a likely cause of this activation.

Base Sequence↗

PubMed1994

Squamous cell carcinoma of the esophagus with mucin-secreting component. Mucoepidermoid carcinoma.

Among 1058 patients with cancer of the esophagus, 20 patients with mucoepidermoid or adenosquamous cell carcinoma of the esophagus and cardia, together defined as squamous cell carcinoma with a mucin-secreting component, were seen over a 10-year period. Their records were reviewed and appropriate comparisons were also made with the more common squamous cell carcinomas and adenocarcinomas. Squamous cell carcinoma with mucin-secreting component comprised 1.9% of all tumors encountered. Clinical features including age, male predominance, symptoms at presentation, length of tumor, and appearance of tumor did not differ from those of squamous cell and adenocarcinoma. The location of these tumors, however, followed that of squamous cell carcinomas, with 55% in the middle third and 25% in the lower third. Adenocarcinomas were found predominantly at the cardia (83%). Operability and resectability rates were higher than those of squamous cell and adenocarcinomas. Primary treatment consisted of resection in 19 of the 20 patients (95%); 18 of them had a one-stage resection and 1 patient had a two-stage resection. Postresection staging showed that 5% had stage I disease, 16% had stage II, and 79% had stage III disease. None of the patients who underwent resection died within 30 days of the operation. The mortality after 30 days was 10.5%. The 1 patient in whom intubation was the primary treatment had distant metastases at the time of presentation (stage IV). The overall median survival was 9.2 months. The median survival for patients who had their tumors resected was 9.5 months. The survival improved to 33 months for curative resection but was only 8.7 months for palliative resection. The 1-, 2-, and 5-year survivals were 46%, 39%, and 0%, respectively. This prognosis was not significantly different from that of patients with squamous cell carcinoma or adenocarcinoma.

Adenocarcinoma↗

PubMed1996

Squamous cell carcinoma of the breast.

OBJECTIVE: To review the mammographic and ultrasonographic features of primary breast cancer containing squamous cell carcinoma. PATIENTS AND METHODS: From medical records for breast cancer patients seen over a 37-year period the authors identified 19 patients with squamous cell carcinoma, for 5 of whom histologic sections and imaging studies were available. The tumours were classified on the basis of histologic findings as pure (in two patients) or predominantly (in three patients) squamous cell carcinoma. Mammograms were available for four of the patients, and the mammographic report only was available for analysis for the fifth. Ultrasonography had been performed for four of the patients; the images were available for two of the patients and the reports only for two. RESULTS: The median age of the patients was 55 years. The mean size of the tumours, all of which were palpable, was 5.0 cm. None of the tumours was connected to the skin, arose in the nipple-areolar complex or was metastatic. On mammography, the margins of all five masses, which were oval in shape, were indistinct and partly well-circumscribed; in three cases, the tumour margin was also partly spiculated. No malignant microcalcifications were seen. The two "pure" squamous cell carcinoma tumours appeared on ultrasonography as solid hypoechoic masses, and two of the predominantly squamous cell carcinoma tumours had both cystic and solid components. At gross pathological examination, four of the tumours (two "pure" and two predominantly squamous cell carcinoma) were cystic, which reflected areas of necrosis and cyst formation. CONCLUSION: Although "pure" or predominantly squamous cell carcinoma is a rare histologic variant of breast cancer that lacks any typical mammographic features, this tumour can be added to the differential diagnosis of cystic breast masses seen on ultrasonography.

Aged↗

PubMedDate not supplied

Proton MR spectroscopy of squamous cell carcinoma of the extracranial head and neck: in vitro and in vivo studies.

PURPOSE: To determine the ability of in vitro one-dimensional and two-dimensional proton MR spectroscopy to help differentiate squamous cell carcinoma of the extracranial head and neck from normal tissues and to correlate the in vitro observations with clinical studies. METHODS: In vitro 1-D and 2-D correlated proton MR spectroscopy (11 T) was performed in tissue specimens of squamous cell carcinoma of the head and neck (n = 19), in normal tissue (n = 13), in metastatic cervical lymph nodes (n = 3), and in a squamous cell carcinoma cell line. In vivo 1-D proton MR spectroscopy (1.5 T) was performed in patients with squamous cell carcinoma (n = 7) and in healthy volunteers (n = 7). The ratio of the areas under the choline (Cho) and creatine (Cr) resonances were calculated for 1-D proton MR spectra for the in vitro tissue studies and correlated with the in vivo studies. Data from in vitro 2-D correlated spectroscopy were analyzed for differences in the presence or absence of various metabolites in samples of tumor and normal tissue. Statistical analysis consisted of 2 x 2 factorial repeated measures analysis of variance (ANOVA), discriminate analysis, and chi2 test. RESULTS: The mean in vitro 1-D proton MR spectroscopic Cho/Cr ratio was significantly higher in tumor than in normal tissue. The difference between the mean ratios appeared to increase with increasing echo time. All in vivo tumor Cho/Cr ratios were greater than the calculated mean in vitro tumor ratio, whereas six of the seven volunteers had no detectable Cho and Cr resonances. Two-dimensional correlated MR spectroscopic data revealed that a variety of amino acids have a significantly greater likelihood of being detected in tumor than in normal tissues. CONCLUSIONS: One-dimensional and 2-D proton MR spectroscopy can help differentiate primary squamous cell carcinoma and nodal metastases containing squamous cell carcinoma from normal tissue both in vitro and in vivo. In addition, 2-D spectroscopy can help identify the presence of certain amino acids in squamous cell carcinoma that are not detected in normal tissue.

Carcinoma, Squamous Cell↗

PubMed1997

Squamous cell carcinoma of esophagus with diffuse mucin-secreting component: a clinicopathologic study.

BACKGROUND: Primary esophageal squamous cell carcinomas with a diffuse mucin-secreting component are not common, and the cases reported are few. The nomenclature for this group of tumors is complex and the histogenesis of these tumors is confused. Therefore, further investigation is needed. METHODS: Twelve cases have been collected from pathology files of Veterans General Hospital-Taipei from 1965 to 1995. Clinicopathologic relationship, histopathological and immunohistochemical features of these cases were analyzed and compared with the reported literature concerning this entity. RESULTS: The age, sex and prognosis for patients of this group, and the size and site of the tumors were not different from that of pure squamous cell carcinoma. The tumors continuously connected with esophageal squamous epithelium, and intraepithelial dysplasia were present in 83% cases. Positive anticarcinoembryonic antigen staining was also demonstrated in squamous epithelium, dysplastic epithelium and tumor cells with either squamous or adenomatous differentiation. CONCLUSIONS: It is believed that esophageal squamous cell carcinoma with diffuse mucin-secreting component is close to the squamous cell carcinoma.

Aged↗

PubMed1991

Coexpression of adult T-cell leukemia-derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium.

Adult T-cell leukemia-derived factor (ADF) is an autocrine interleukin-2 receptor-inducing factor produced by human T-lymphotropic virus-1 (HTLV-1)-transformed lymphocytes, which has a high structural homology with an endogenous dithiol reducing coenzyme, thioredoxin. Its localization was investigated immunohistochemically in the cervix, using normal tissue (27 samples) and squamous neoplastic tissue (three condylomas, 42 cervical intraepithelial neoplasia [CIN] samples, 34 invasive squamous cell carcinoma samples). The expression of human papillomavirus (HPV) DNA was also studied in serial sections of the same subjects. Normal squamous cells and glandular cells of the cervix were negative for ADF. However, intracytoplasmic and/or intranuclear ADF-positive cells were usually found in the intermediate and superficial layers of the neoplastic squamous epithelium of condylomas (three of three cases) and CIN (35/42 cases). HPV DNA was detected in all condylomas and in 27 of 42 CIN specimens. HPV DNA-positive cells were usually localized in the intermediate and superficial layers of the neoplastic squamous epithelium. These HPV DNA-positive cells were also positive for ADF. Invasive squamous cell carcinoma was also positive for ADF (24/34 cases) and HPV DNA (11/34 cases). The coexpression of HPV DNA and ADF was observed in all HPV DNA-positive cases. Coexistence of HPV DNA and ADF immunopositivity in neoplastic squamous cells of the cervix suggests that ADF expression closely reflects the intracellular event on HPV DNA replication.

Adult↗

PubMed2003

Urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix.

BACKGROUND: The large data bases of the Dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix. METHODS: Six cytology laboratories in the context of the Dutch cervical screening program screened over 190,000 cervical smears. Urbanization (place of residence) data were derived from postal codes. All smears were coded with the Dutch national coding system, the Dutch national classification system KOPAC, in which squamous abnormalities are coded S4-S9, and glandular cell changes are coded G4-G9. From the scores per 1000 screened women, the relative risk (RR) of living in a large city compared with living in rural areas was calculated. To investigate a trend in incidence in relation to urbanization, the Schaafsma method was used. RESULTS: Of the smears with positive cytology, mild squamous dysplasia (S4) had the highest incidence per 1000 screened women (4.32), and the lowest incidence was found for adenocarcinoma (in situ; G7/G9; RR, 0.07). The RR for urban women ranged from 1.73 for moderate squamous dysplasia (S5) to 7.55 for adenocarcinoma (in situ; G7/G9). For smears with positive cytology for both squamous and glandular abnormalities, the Schaafsma method indicated a significant positive trend. CONCLUSIONS: The incidence of squamous and glandular abnormalities are maximal in women who live in a large city, which, in The Netherlands, is where there also is a population at high risk for human papillomavirus and bacterial vaginosis.

Adenocarcinoma↗

PubMed1991

Squamous-cell carcinoma antigen (SCC-A) values related to clinical outcome of pre-invasive and invasive cervical carcinoma.

The serum concentration of squamous-cell carcinoma antigen (SCC-A), a subfraction of tumour antigen, was determined by RIA from healthy donors (control group) and from patients with malignant cervical disease. Ninety-six percent (173/180) of the healthy patients had squamous-cell carcinoma antigen serum levels below 2 ng/ml. Ten of 70 (14.3%) patients with CIN III, 53.8% (34/62) of patients with invasive squamous-cell carcinoma stage I, 85.8% (30/35) with stage II and 96.5% (27/28) with stage III/IV had squamous-cell carcinoma antigen serum levels above 2 ng/ml. We observed that 22.5% (11/49) of patients with a tumour volume below 10 ml and 92.6% of patients with a tumour volume greater than 10 ml had squamous-cell carcinoma antigen levels above 2 ng/ml (p less than 0.005). SCC-A was correlated with recurrence or progressive disease in 90.0% of cases. Other risk factors such as depth of invasion, microscopic parametrial involvement, lymphatic and/or vascular space permeation and histological grade were not correlated with squamous-cell carcinoma antigen. Furthermore, this marker increased 4.3 +/- 2.7 months before clinical evidence of recurrence or progressive disease. We conclude that serial serum levels of squamous-cell carcinoma antigen provide a means for early detection of recurrence or progressive disease. This tumour marker might also be useful for monitoring the treatment effects and has some prognostic value.

Antigens, Neoplasm↗

PubMed1992

Image analysis in the discrimination of verrucous carcinoma and squamous papilloma.

Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in these two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P less than 0.001) by an uncorrelated t-test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 microns 2 and the latter 184 microns 2. Squamous cell carcinomas differed from the other two neoplasms by their large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 microns 2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 microns 2 supports a diagnosis of squamous papilloma.

Adult↗

PubMed1993

Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett's epithelium.

Metaplastic columnar epithelium replaces the normal squamous epithelium in Barrett's esophagus. We characterized the surface epithelial cells of the junction between squamous and Barrett's epithelium using scanning electron microscopy and light microscopy. In four biopsy specimens from the squamous-Barrett's junction in three patients, we found a distinctive cell type having features intermediate between those of squamous and columnar epithelium. Its distinguishing characteristic is the presence on its surface of two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous mucosa). The surface characteristics of this newly recognized cell were strikingly similar to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. We also examined 28 biopsies of the gastroesophageal junction area from 14 patients with and without a history of heartburn but with no evidence of Barrett's esophagus. None of these biopsies showed the distinctive cell. We hypothesize that this distinctive cell represents an intermediate step in either the development or the healing of Barrett's epithelium, during which surface characteristics of two different cell types, columnar and squamous, coexist on the same cell.

Aged↗

PubMedDate not supplied

The use of an in vitro submerged keratinocyte model to predict induction of squamous metaplasia.

An in vitro submerged keratinocyte model of squamous metaplasia (SQ) in epithelia is being developed to assess the risk associated with exposure to certain environmental agents. Tracheobronchial epithelium (TBE) in vivo can respond to airborne environmental insult by becoming squamous. Epidemiological evidence suggests that cigarette smoke is capable of inducing this change. Retinoic acid has been shown to maintain cells in the mucociliary state. SQ is considered protective and adaptive but potentially preneoplastic if unrelenting and is used histologically in the diagnosis of squamous cell carcinoma. SQ is characterised by upregulation of the expression of transglutaminase I (TGI), TGI activity leading to the formation of isopeptide cross-linked envelopes and replacement of the mucociliary cell type with non-polar squamous cells out of contact with the basal lamina. The ability of the in vitro keratinocyte submerged model to predict the squamous metaplastic response in vivo has been investigated in vitro using TG catalysed fluorescein cadaverine incorporation as a measure of cross-linked envelope formation, Alamar blue conversion to measure viability and Coomassie blue incorporation to measure total cellular protein. The modulation of the squamous condition by retinoic acid (RA), cigarette smoke condensate (CSC) and nicotine has been assessed in keratinocytes cultured in Green's medium. RA inhibited FC incorporation by 95% at 1 x 10(-5) M and simultaneously increased cell viability providing evidence to support its role in the regulation of the non-differentiated state. Nicotine (0-1 mg/ml) induced a dose-dependent increase in viability at 6 days, a response that was accompanied by an increase in FC incorporation at 12 days. CSC (0-5 microg/ml) increased FC incorporation after 12 days. Hence, nicotine modulated the squamous condition by up-regulating TGI activity following a period of hyperactivity. CSC induced a gradual change to the differentiated state and RA served to maintain the cells in an undifferentiated state.

Animal Testing Alternatives↗

PubMed1993

Morphology and histogenesis of squamous cell metaplasia of the rat lung after chronic exposure to a pyrolized pitch condensate and/or carbon black, or to combinations of pyrolized pitch condensate, carbon black and irritant gases.

Female Wistar rats were exposed to different concentrations of a pyrolized pitch condensate and/or carbon black particles and/or a combination of irritant gases for 18 hours/day, 5 days/week for 10 months, followed by a clean air period of up to 20 months. Bronchiolo-alveolar hyperplasia and squamous metaplasia were important components of the resulting lesions. Squamous metaplasia and associated hyperplasia was investigated by routine histology, scanning and transmission electron microscopy, and by immunohistochemical detection of various cytokeratins (CKs). Intensely CK positive squamous metaplasia lacking a distinct stratum spinosum was distinguishable from squamous metaplasia with a distinct stratum spinosum that reacted weakly CK positive or CK negative. The CK positive type was histologically characterized by narrow intercellular spaces, the weakly CK positive or CK negative type had markedly enlarged intercellular spaces. Differentiated hyperplastic epithelium and the normal lung parenchyma reacted CK negative. In poorly differentiated hyperplasia of the alveolar type associated with squamous metaplasia scattered cells with characteristics of squamous differentiation were detected. Ultrastructurally these cells showed increased amounts of filament bundles and immunohistochemically a positive reaction with the CK antibody. These cells were regarded as precursor stages of squamous metaplasia of the lung periphery in rats.

Animals↗