Biomedical subjects

H J Altermatt

Publications and source records attributed to H J Altermatt.

At least 19 recordsLinked to original sources

PubMed2005

Correlation between the tumoral expression of beta3-integrin and outcome in cervical cancer patients who had undergone radiotherapy.

Integrins are cell-surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Besides playing an important role in tumour angiogenesis, beta3-integrin is also expressed in several types of epithelial cancer cells. It was the purpose of the present study to evaluate the prognostic value of beta3-integrin expression in patients with cervical cancer. Biopsies were taken from 82 patients with squamous cell or adenocarcinomas of the uterine cervix who had undergone external-beam radiotherapy with or without brachytherapy. These tissue samples were analysed immunohistochemically for the expression of beta3-integrin. The impact of immunoreactivity for beta3-integrin on survival end points was assessed by univariate and multivariate analyses, and its correlation with clinicopathological characteristics evaluated by crosstabulations. beta3-integrin was expressed in 61% (50 of 82) of the patients. Kaplan-Meier curves revealed local progression-free survival, distant metastasis-free survival and cause-specific survival to be significantly shorter (P-values according to the log-rank test: 0.002, 0.04 and 0.01, respectively) in patients with beta3-integrin expression. The prognostic impact of this parameter was even higher than for other well-known prognostic parameters and remained statistically significant in the multivariate analyses. beta3-integrin, which is expressed in the majority of patients with advanced cervical cancer, has a significant prognostic impact on outcome according to univariate and multivariate analyses.

Adenocarcinoma↗

PubMed2001

The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression.

Genes of the polycomb group function by silencing homeotic selector genes that regulate embryogenesis. In mice, downregulation of one of the polycomb genes, bmi-1, leads to neurological alterations and severe proliferative defects in lymphoid cells, whilst bmi-1 overexpression, together with upregulation of myc-1, induces lymphoma. An oncogenic function has been further supported in primary fibroblast studies where bmi-1 overexpression induces immortalization due to repression of p16/p19ARF, and where together with H-ras, it readily transforms MEFs. It was the aim of this study to assess the expression of bmi-1 in resectable non-small cell lung cancer (NSCLC) in association with p16 and p14ARF (=human p19ARF). Tumours (48 resectable NSCLC (32 squamous, 9 adeno-, 2 large cell, 4 undifferentiated carcinomas and 1 carcinoid); stage I, 29, II, 7, III, 12; T1, 18, T2, 30; differentiation: G1 12, G2 19, G3 17) were studied by immunohistochemistry for protein expression and by comparative multiplex PCR for gene amplification analysis. In tumour-free, normal lung tissue from patients, weak - moderate bmi-1 staining was seen in some epithelial cells, lymphocytes, glandular cells and in fibroblasts, whereas blood, endothelial, chondrocytes, muscle cells and adipocytes did not exhibit any bmi-1 expression. In tumours, malignant cells were negative/weakly, moderately and strongly positive in 20, 22 and 6 cases, respectively. As assessed by multiplex PCR, bmi-1 gene amplification was not the reason for high-level bmi-1 expression. Tumours with moderate or strong bmi-1 expression were more likely to have low levels of p16 and p14ARF (P = 0.02). Similarly, tumours negative for both, p16 and p14ARF, exhibit moderate-strong bmi-1 staining. 58% of resectable NSCLC exhibit moderate-high levels of bmi-1 protein. The inverse correlation of bmi-1 and the INK4 locus proteins expression (p16/p14ARF) supports a possible role for bmi-1 misregulation in lung carcinogenesis.

Aged↗

PubMed2001

Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast.

BACKGROUND: Axl, a member of a family of receptor tyrosine kinases characterized by an extracellular domain resembling cell adhesion molecules and an intracellular conserved tyrosine kinase domain has been reported to induce cell proliferation and transformation. In mice, axl is expressed in the normal mammary gland and over-expressed in aggressive mammary tumors. PATIENTS AND METHODS: We have investigated the expression of axl immunohistochemically in 23 normal human breast samples and in 111 consecutive breast carcinomas. Expression of axl was correlated with tumour characteristics (lymph node involvement, stage, grade) and immunohistochemical expression of ER, PR, Ki-67 and c-erbB-2. RESULTS: In normal tissue, axl localizes to the membrane of breast epithelial cells. Axl protein shows membrane associated staining in high correlation (P = 0.004) with the expression of the estrogen receptor (ER). Axl expression was found in a subset of breast carcinomas and was also correlated with high significance (P < 0.0001) with the presence of ER. CONCLUSION: Our results suggest that axl may serve as a mediator of estrogen stimulation preventing the completion of the breast epithelial life cycle and that estrogen induced axl expression may give a survival signal to cancerous cells, preventing them from dying through apoptosis.

Adolescent↗

PubMed2001

EGFR dependent expression of STAT3 (but not STAT1) in breast cancer.

STAT proteins constitute a family of transcription factors whose activation by cytokine and non-cytokine receptors leads to tyrosine phosphorylation, dimerization and translocation from the cytoplasm to the nucleus. In the nucleus they activate the transcription of specific genes by binding to consensus DNA elements. STATs 1 and 3 can be activated by both cytokine and non-cytokine receptors, and bind as homodimers or heterodimers to viral simian sarcoma virus (sis)-inducible elements such as that found in the c-fos promoter. Activation of c-Src and EGF receptor tyrosine kinases is associated with progression of breast cancer. Both these events lead to activation of STAT proteins, Src kinases activate STAT3 dependent transcription in mammary epithelial cells and EGF receptor activation can lead to activation of STATs 1 and 3. STAT3 activation has been demonstrated to have a role in oncogenesis and increasingly, activated STAT proteins are found to be activated in human cancer. In this study we describe detailed immunohistochemical analysis of nuclear and cytoplasmic STATs 1 and 3 expression in primary breast carcinomas and correlate this with EGFR, HER2, p53, ER, PR, p21/waf1, Bcl-XL and Ki-67 expression. We also compared expression between normal and tumor tissue. We report here a highly significant correlation between nuclear STAT3 expression and breast cancers compared to normal tissue. We also report a very strong correlation between nuclear STAT3 and EGFR expression in breast cancers. These data clearly demonstrate a strong association between STAT3 activation and breast tumorigenesis and strengthen the assertion that STAT3 activation may play an important role in the tumorigenic conversion of breast tissue mediated by tyrosine kinase signaling pathways.

Adenocarcinoma, Mucinous↗

PubMed2000

Differential expression of p73 splice variants and protein in benign and malignant ovarian tumours.

The p73 gene encodes a protein with substantial structural and functional similarities to the tumour-suppressor p53. Alternative splicing of p73 mRNA leads to expression of 6 known RNA species and proteins (alpha, beta, gamma, delta, epsilon, zeta). We analysed the expression of these splice variants in ovarian adenocarcinoma by RT-PCR followed by detection of amplicons with the Southern technique and by immunoblot in 32 malignant and benign epithelial ovarian tumour specimens and 3 ovarian adenocarcinoma cell lines (A2780, 2008, OVCAR-3). p73alpha mRNA was expressed in all 17 ovarian cancer specimens, and 14 of 17 expressed at least 3 splice variants. In contrast, a different expression pattern was present in the ovarian adenomas: p73alpha was detected in 6 of 12 benign tumours, and only 1 adenoma expressed 3 splice variants. p73 protein was expressed in 9 of 16 ovarian cancer specimens, in all cell lines and in 1 of 3 borderline tumours. In contrast, none of 9 ovarian adenomas expressed detectable amounts of p73 protein. Expression of p73 mRNA and protein was not correlated with FIGO stage and histological grade, but we observed a significant correlation with over-expression of p53 protein. In summary, epithelial ovarian cancers express a more complex p73 isoform pattern and higher levels of p73 mRNA and protein than ovarian adenomas.

Adenocarcinoma↗

PubMed2000

Hormone-dependent nuclear localization of the tyrosine kinase iyk in the normal human breast epithelium and loss of expression during carcinogenesis.

iyk, a member of the frk family of non-receptor tyrosine kinases, was originally isolated from normal mouse mammary glands and is characterized by a nuclear localizing signal within the SH2 domain. We have investigated the expression and subcellular localization of iyk in the normal human breast and in malignant breast diseases. Immuno-histochemical analyses revealed that in normal tissue iyk localizes to both cytoplasmic and nuclear compartments of breast epithelial cells. The subcellular distribution was dependent on the hormonal state, being mostly cytoplasmic during the follicular, proliferative phase of the menstrual cycle, whereas frequent nuclear staining was observed in the resting stages during the luteal phase and, most prominently, after menopause. Strikingly, invasive carcinomas, irrespective of tumor type or hormonal status of the patient, exhibited almost complete loss of iyk expression in both the cytoplasm and the nucleus. In contrast, in situ breast carcinomas from post-menopausal patients showed a clear reduction of the nuclear iyk localization while retaining cytoplasmic staining. Our results indicate that iyk expression is gradually lost during carcinogenesis; thus, iyk may be classified as a tumor-suppressor gene.

Adult↗

PubMed2000

Paraneoplastic cerebellar degeneration in pediatric Hodgkin disease.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication in adults with extracerebral neoplasms. It is characterized by a diffuse cerebellar dysfunction, usually leading to severe neurological sequelae. In childhood, this complication is extremely rare. We report on PCD as primary manifestation of Hodgkin disease (HD) in a thirteen-year old boy. On magnetic resonance imaging, irreversible atrophy of the cerebellum developed within three months. Antibodies against Purkinje cells were detectable at diagnosis and normalised after successful treatment of the lymphoma. Cerebellar symptoms, however, only partially resolved. The necessity of a search for a malignant tumour is emphasised in the presence of an otherwise unexplained, subacutely developing, diffuse cerebellar dysfunction.

Adolescent↗

PubMed2000

p21 is associated with cyclin D1, p16INK4a and pRb expression in resectable non-small cell lung cancer.

p21 (p21WAF1/CIP1) is involved in cell cycle regulation, as an inhibitor of cyclin dependent kinases (CDK2, CDK4 and CDK6). However, subsequent in vitro studies have suggested that p21 may influence this process by an additional mechanism, in particular through the regulation of cyclin D1 subcellular localisation. This study of primary resectable non-small cell lung cancer (NSCLC) was designed to examine p21 functions in association with the expression of cyclin D1 (including its subcellular localisation), p16INK4a and pRb. p21 expression was examined in 50 NSCLC (stage I-IIIA) and in several normal lung samples all of which had previously been studied for cyclin D1 (DNA, RT-PCR, immunostaining), p16INK4a (DNA, RT-PCR, immunostaining), and pRb (immunostaining). As assessed by immunoblotting and immunostaining, p21 was expressed at low levels in normal lung tissue with immunoreactivity seen in a small number of bronchial epithelial cells only. In NSCLC, p21 expression (> or =10% of positive cells) was observed in 42% (21/50) of cases. High p21 expression was associated with well differentiated tumours (p = 0.01) and cyclin D1 nuclear staining (p = 0.02). Furthermore, we found an inverse correlation with p16INK4a (p = 0.004) and a direct correlation with pRb expression (p = 0.02). Risk of relapse was associated with p16INK4a and p21 status with no relapse in patients with normal p16INK4a and p21. Our results confirm that a large number of NSCLC have a low level of p21 expression. The associations of p21 and nuclear cyclin D1, pRb, p16INK4a support the relevance of pathways linked to lung carcinogenesis that involve p21 but may act in addition to direct CDK inhibition.

Aged↗

PubMed2000

Clear cell adenocarcinoma of the cervix associated with a rare genitourinary malformation.

BACKGROUND: Cervical adenocarcinoma and genitourinary malformations are relatively common disorders, yet their coexistence is rare. CASE: A 49-year-old woman developed clear cell adenocarcinoma in the atretic hemicervix of a communicating uterus type 7 and had ipsilateral renal agenesis. Compared with the unaffected right hemicervix, only the tumor-involved glands of the atretic left hemicervix contained ciliated tuboendometrial cells. Four and a half years after radical hysterectomy and pelvic radiation, she showed no evidence of recurrence. CONCLUSION: In contrast to current opinion, communicating uteri type 7 are associated with ipsilateral renal agenesis. Our histologic findings support the hypothesis that tuboendometrial cells are the cells of origin for cervical clear-cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗

PubMed1999

Expression of apoptosis regulatory proteins of the Bcl-2 family and p53 in primary resected non-small-cell lung cancer.

Proteins of the Bcl-2 family as well as p53 are important regulators of apoptosis. Alterations in the expression of these proteins can contribute to the formation of cancer, as well as influence tumour response to chemo- and radiotherapy. We used antibodies specific for the human Bcl-2, Mcl-1, Bax, Bak and p53 proteins to examine the expression of these apoptosis-regulating genes in 49 archival specimens of patients with radically resected non-small-cell lung cancer (NSCLC). Tumour cells containing immunostaining for the antiapoptotic proteins Bcl-2 and Mcl-1 were present in 31% and 58% of the cases evaluated, respectively, whereas immunopositivity for the proapoptotic proteins Bax and Bak was found in 47% and 58% of the samples. p53 immunopositivity was detected in 61% of the samples. The expression of Bcl-2 and p53 and the expression of Mcl-1 and Bax showed a positive association (P = 0.02 and P = 0.06 respectively), whereas the expression of Bax was inversely related to p53 (P = 0.008). The expression of Bcl-2 had a negative influence on relapse-free survival in this population of primary resected NSCLC patients (P = 0.02). The expression of p53 and Bcl-2 was significantly associated with metastasis-free survival (P < 0.01). Only patients with p53-positive tumours developed metastases during the follow-up period. Our results establish the frequent expression of the Bcl-2 family proteins Bcl-2, Mcl-1, Bax and Bak in NSCLC. It can be expected that Bcl-2 family members have no straightforward impact on clinical outcome in this disease because their interactions in the regulation of apoptosis are complex.

Apoptosis↗

PubMed1999

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.

Adenocarcinoma↗

PubMed1998

Expression of p16INK4a/p16alpha and p19ARF/p16beta is frequently altered in non-small cell lung cancer and correlates with p53 overexpression.

The CDKN2 locus expresses two different mRNA transcripts, designated alpha and beta. The protein product of the alpha transcript is the cell cycle inhibitor and tumour suppressor p16INK4a. The beta transcript is translated in an alternate reading frame (ARF) and in humans encodes a 15 kDa protein (p19ARF). Immunohistochemical and Western analysis of p16INK4a has shown that the protein is downregulated in a significant number of tumours, but less is known on the expression of the p19ARF. We have examined the expression of p16INK4a and p19ARF in resectable non-small cell lung cancer (NSCLC) by immunostaining (n=49) and multiplex RT-PCR (n=28). In order to investigate the mechanism responsible for p16INK4a downregulation, exon 1alpha methylation was analysed in a PCR-based assay. Of 49 tumours examined by immunostaining, 24 and 20 tumours expressed p16INK4a and p19ARF at nil to low levels, respectively. p19ARF was localized primarily to the nuclei of tumour cells, but was also seen to varying degrees in nuclei of lymphocytes, chondrocytes, fibroblasts, and epithelial cells. No tumour with normal p16INK4a had decreased p19ARF expression. Among 16 tumours with nil to low p16INK4a expression, 11 tumours exhibited full methylation of at least one site within exon 1alpha and these tumours showed normal p19ARF expression. In contrast, no methylation of exon 1alpha was observed in five tumours which also lacked p19ARF. In normal lung, p16INK4a and p19ARF were not expressed at detectable levels, the multiplex RT-PCR results were balanced, and sites within exon 1alpha were strongly methylated. In tumours, imbalanced multiplex RT-PCR data (p16INK4a<p19ARF) predicted methylation of exon 1alpha (P=0.0006) as well as downregulation of p16INK4a. p19ARF downregulation was inversely correlated with p53 overexpression (P=0.025), whilst negative immunostaining for p16INK4a was inversely correlated with pRb down-regulation (P=0.003) and directly correlated with p53 overexpression as assessed by immunostaining (P=0.015). Our results show that: (1) p16INK4a and p19ARF expression are altered in almost half of resectable NSCLC; (2) methylation within exon 1alpha is a frequent, but not the only mechanism of p16INK4a downregulation; and that (3) the inverse association of p19ARF and p53 alteration is consistent with a linked pathway.

Aged↗

PubMed1998

Apoptosis during castration-induced regression of the prostate is Fos dependent.

Apoptotic cell death was shown to be accompanied or preceded by an elevated expression of the c-fos protooncogene and DNA binding activity of transcription factor AP-1. We used Fos-deficient mice to study the role of c-Fos during programmed cell death in the prostate. In normal mice apoptosis is induced in the prostate within 2-4 days after castration. Histological features of reduced secretory activity and morphological signs of programmed cell death become obvious. No apparent decrease in secretory activity and no epithelial cell death were observed in Fos-deficient animals after castration. Fragmentation of nuclear DNA was measured by in situ terminal transferase reaction. DNA fragmentation was observed in the prostate epithelium of control mice after castration whereas no similar fragmentation was found in Fos-deficient animals. After castration an AP-1 complex accumulated in the prostate of Fos deficient mice which mainly consists of FosB, Fra-2 and JunD whereas in control animals the AP-1 complex in addition contained c-Fos. Our data strongly suggest that c-Fos is required for programmed cell death of prostate epithelial cells.

Animals↗

PubMed1998

[Sentinel lymphadenectomy: an alternative to axillary lymphadenectomy in breast carcinoma].

BACKGROUND: Axillary lymph node status is an important determinant of prognosis in breast cancer. However, lymphadenectomy does not benefit half of the patients in whom axillary nodes are free of disease. Sentinel lymph node biopsy is a new technique which allows accurate staging of breast carcinoma without performing total axillary dissection. We describe our experience with the introduction of sentinel lymphadenectomy. METHODS: Thirty-seven sentinel lymphadenectomies were performed in 35 patients referred to the Department of Obstetrics and Gynaecology of the University of Berne between December 1997 and June 1998. Mapping procedures were performed using a combination of vital blue dye with preoperative lymphscintigraphy with 99mTechnetium-labelled colloidal albumin and intraoperative use of a gamma probe. Complete axillary lymphadenectomy was then performed in 34 patients. RESULTS: One or more lymph nodes were identified in 33 of 37 procedures (89%). With the combination of both localisation techniques the sentinel nodes were identified in all (100%) of the last 19 patients. Sentinel and non-sentinel lymph nodes were always concordant. In this series the negative predictive value is 100% (95% confidence interval: 87.7%-100%). Metastases were found in the sentinel node in 11 of 30 patients (37%). From these 11 patients, 3 (27%) had micrometastases. CONCLUSIONS: Histopathologic examination of the sentinel lymph node accurately predicts the axillary lymph-node status. Patients with sentinel nodes free of metastases could avoid the unnecessary peri- and postoperative complications of complete axillary dissection. Further studies are needed to assess whether the improved diagnosis of micrometastases by sentinel lymphadenectomy influences the long-term prognosis of breast cancer.

Adult↗

PubMed1998

Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology.

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors

Adenocarcinoma↗

PubMed1998

Amyloidomas of the nervous system: a monoclonal B-cell disorder with monotypic amyloid light chain lambda amyloid production.

BACKGROUND: Amyloidomas or localized tumor-like amyloid deposits rarely affect the nervous system. To the authors' knowledge, no comprehensive studies on central and peripheral nervous system amyloidomas have been published. The amyloid subtype of amyloidomas of the nervous system only recently was characterized and almost invariably was found to be of amyloid light chain (AL) lambda type. The nature of the plasma cell population responsible for AL amyloid production has not been investigated further. METHODS: The current analysis included the clinical findings, neuroimaging characteristics, and pathology of seven amyloidomas (four cerebral and three involving peripheral nerves). All were subjected to histochemical staining (Congo red, thioflavine S) and to immunohistochemical study using primary antibodies detecting serum amyloid component P, serum amyloid protein A (SAA), transthyretin, beta2 microglobulin (beta2m), and free immunoglobulin (Ig) light chain. For the detection of mRNA of light chain Ig, fluorescein-conjugated kappa and lambda mRNA oligonucleotide probes were used. For the assessment of B-cell clonality, polymerase chain reaction (PCR) was applied on extracted DNA from two cases using VH FRIII and JH primers. Two cases were assessed ultrastructurally. RESULTS: All amyloidomas were organ restricted and unrelated to systemic amyloidosis. The clinical symptoms of the cerebral lesions were nonspecific, whereas neurologic deficits were noted in the distribution of the involved peripheral nerves. Cerebral deposits, either solitary or multiple, were associated spatially with the choroid plexus and secondarily extended into white matter. All peripheral nerve amyloidomas involved the gasserian ganglion of the trigeminal nerve. Imaging by computed tomography and magnetic resonance imaging scans revealed hyperdense and contrast-enhancing mass lesions unassociated with significant edema. Immunohistochemically, the amyloid was present in the interstitium and within the walls of the intralesional vessels, was invariably of AL lambda subtype, and was negative for free Ig kappa light chains, SAA, transthyretin, and beta2m. Plasma cells along the perivascular sheaths and occasionally squeezed between amyloid masses showed no cytologic atypia. In situ hybridization for Ig light chain mRNA reflected a massive preponderance of lambda-producing cells. PCR revealed monoclonal rearrangement of the heavy chain Ig gene. CONCLUSIONS: The results of the current study provide strong support for the concept that amyloidomas of the nervous system are neoplasms of an AL lambda-producing B-cell clone capable of terminal differentiation. Nevertheless, all seven patients lacked clinical evidence of an aggressive or systemic lymphoplasmacytic neoplasm. Unlike plasmacytomas, the relatively indolent course of most nervous system amyloidomas is reminiscent of the similarly indolent biologic behavior of extranodal, low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Adult↗

PubMed1998

Endobronchial photodynamic therapy: comparison of mTHPC and polyethylene glycol-derived mTHPC on human tumor xenografts and tumor-free bronchi of minipigs.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) with mTHPC and polyethylene glycol-derived mTHPC (pegylated mTHPC) was compared on nude mice bearing human squamous cell carcinoma and adenocarcinoma xenografts. The same treatment regimens were applied to the bronchi of tumor-free minipigs to assess injury to normal tissue. STUDY DESIGN/MATERIALS AND METHODS: Laser light (652 nm, 20 J/cm2) was delivered as surface radiation to the xenografts 4 days after intraperitoneal administration of 0.1 mg/kg mTHPC or an equimolar dose of pegylated mTHPC, respectively. The extent of tumor necrosis was assessed by histomorphometry. Endobronchial PDT was performed on the bronchi of minipigs with the same drug and light doses at drug-light intervals ranging from 12-96 hr. RESULTS: Both sensitizers produced larger necrosis of squamous cell carcinoma and adenocarcinoma xenografts than was observed in untreated controls (P < 0.005). Pegylated mTHPC led to larger tumor necrosis than mTHPC in squamous cell carcinoma (P < 0.001), but not in adenocarcinoma xenografts. mTHPC-PDT resulted in ulceration and necrosis of bronchial mucosa in minipigs at drug-light intervals ranging from 12-48 hr, which was not observed after use of pegylated mTHPC. CONCLUSIONS: In this setting, pegylated mTHPC had advantages as a photosensitiser compared to mTHPC.

Adenocarcinoma↗

PubMed1998

Anti-neuronal nuclear autoantibodies, types 1 and 2: their utility in the study of tumors of the nervous system.

This is a comprehensive immunohistochemical study of selected archival tumors of the nervous system applying human anti-neuronal nuclear autoantibodies of types 1 and 2 (ANNA-1 and -2), serum markers of paraneoplastic syndromes associated primarily with small cell lung cancer (SCLC). Neither ANNA-1 nor ANNA-2 bound to glial tumors regardless of histological grade and subtype; instead they labeled neurons in overrun normal parenchyma. Central neurocytomas and the neuronal components of mixed glioneuronal tumors were also immunoreactive for both. In addition, varying proportions of tumor cells were stained in dysembryoplastic neuroepithelial tumor, subependymal giant cell astrocytoma (SEGA), tuber and neuroblastoma. All other tumors were nonreactive, namely choroid plexus papilloma, pituitary adenoma, pineocytoma, pheochromocytoma, thymic and pulmonary carcinoid, chordoma, meningioma, schwannoma and metastatic melanoma. SCLC was immunonegative for ANNA-1 and ANNA-2 in paraffin preparations, but displayed strong immunoreactivity for both in frozen sections: this discrepancy was not observed in other tumors studied. In conclusion, the human IgG autoantibodies ANNA-1 and ANNA-2 provide novel tools for studying the cytogenesis of tumors of the nervous system in that they permit the identification of both normal and neoplastic, poorly differentiated and small neuronal cells that may escape detection using commercially available anti-neuronal antibodies.

Antibodies, Antinuclear↗