Normalization of the psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in Turkey.

AIM: To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and evaluate the prevalence of minimal hepatic encephalopathy (MHE) among Turkish patients with liver cirrhosis. MATERIALS AND METHODS: One hundred and eighty-five healthy subjects and sixty patients with liver cirrhosis without overt hepatic encephalopathy were included in the study. All subjects underwent psychometric tests, which include number connection test-A and B (NCT-A/B), serial dotting test (DST), line drawing test (LDT), and digit symbol test (DST) in the same day. The variables that affected the results of the test were included in the multiple linear regression models and formulas were constructed to predict the expected results for each tests. RESULTS: The results of all PHES tests, except the LDT in the cirrhotic group were significantly different than center of gravity (CG) (P < 0,001). The score of PHES in the cirrhotic group was -2,18 ± 3,3 (median -2; range: 11 to +4), significantly lower than CG (-0.31 ± 2.18 [median, 0; range, -8 to +5]) (P < 0.001). the cutoff of PHES was set -4 point. Therefore, 19 of the 60 cirrhotic patients were diagnosed with MHE (31.6%). Among the patients with MHE, 11 (11/45, 24,4%) had Child-Pugh classification (CTP) A and 8 (8/15, 53.3%) had CTP B. No differences in age and education years were found between the MHE and non-MHE groups (P > 0.05). CONCLUSION: Turkish PHES normograms have been developed for detecting patients with MHE. Future multicenter national studies are needed to validate widely applicable norms.

Differential expression of LOXL4 in normal and tumour tissue samples of laryngeal squamous cell carcinoma.

OBJECTIVE: Head and neck cancer is the sixth most common cancer in worldwide with an increasing incidence rate in recent years. LOXL4 is expressed in several tissues, and its expression has been shown to display a significant correlation with local lymph node metastasis. In this study, we aimed to explore the LOXL4 expression level in metastatic and non-metastatic LSCC tissues and to determine its prognostic significance. STUDY DESIGN: Basic science research study. SETTING: University hospital. PARTICIPANTS: A total of 40 patients were included in the study. MAIN OUTCOME MEASURE: LOXL4 expression status in metastatic, non-metastatic LSCC and normal tissue samples was investigated by quantitative reverse-transcription PCR. RESULTS: We demonstrated that LOXL4 was significantly overexpressed in LSCC tumour tissue samples in comparison with the corresponding normal tissues (P < 0.001); however, no significant relationship has been found between LOXL4 expression and either the metastatic potential or the T classification of the specimens. CONCLUSIONS: Although expression of LOXL4 is not statistically associated with neck metastases, we showed that LOXL4 expression significantly increased in laryngeal cancer.

Comparison of immunogenicity for Sinovac-CoronaVac vaccine vs. natural infection during cancer treatment.

OBJECTIVE: Efficacy of the COVID-19 vaccines in cancer patients, especially during their active treatment, are lacking. Most of the studies in the literature compared the immunity in cancer patients with a cross-sectional cohort or retrospectively. Our study investigated Sinovac-CoronaVac COVID-19 vaccine immunogenicity and compared it with natural COVID-19 disease in cancer patients during their cancer therapy. PATIENTS AND METHODS: A total of 111 patients with cancer and who are on active treatment were included in the study. This is a single-center study and was designed prospectively. Two group of patients were included in the study, natural disease and vaccinated group. RESULTS: A total of 111 patients were included in the study, 34 of whom had natural COVID-19 disease. Antibody levels following the first dose vaccine were 0.4 (0-1.9) U/ml while after the second dose of vaccine were 2.6 (1.0-7.25) U/ml. Immunogenicity levels were 82.4% in the natural disease group and 75.8% in the vaccinated group after the second shot of the vaccine. Immunogenicity rate was significantly higher in non-chemotherapy (receiving immunotehrapy/targeted therapy or biologic agent) group compared to chemotherapy drug (92.9% vs. 63.3%, p=0.004). There was a difference between the antibody levels following the first and second vaccination [median (IQR): 0.3 (0-1.0) and 3.3 (2.0-6.7), p=0.001, respectively]. CONCLUSIONS: The present study revealed that the Sinovac-CoronaVac vaccine showed an acceptable immunogenicity following two shots in cancer patients who were receiving active systemic therapy. On the other hand, natural disease immunogenicity was higher than vaccinated group.

How confocal laser endomicroscopy can help us in diagnosing gastric lymphomas?

Primary gastric diffuse large cell lymphoma is one of the most common extranodal lymphomas of the gastrointestinal system. Diagnosing gastrointestinal lymphomas can be difficult, since there is no pathognomonic sign in endoscopy to distinguish it from other malignancies. In some cases biopsy can be non-diagnostic. Therefore, multiple endoscopic examinations and biopsies can be necessary. With using confocal endomicroscopy, histology of the tissue can be seen in vivo and a range of diseases can be identified by using this technique. We are presenting a case, which is diagnosed as primary gastric diffuse large cell lymphoma during the evaluation of erythema nodosum etiology. We want to emphasize the role of confocal laser endomicroscopy for in vivo diagnosis of gastric lymphoma and directing the endoscopist for sampling the diseased mucosa. Confocal endomicroscopy decreases non-diagnostic rates in endoscopic biopsy and can be performed successfully in cases of gastric lymphoma. Pit patterns of gastric lymphoma, ring cell gastric carcinoma and gastric adenocarcinoma are similar. To best of our knowledge, this case is the fifth case of confocal laser endomicroscopy aided in diagnosing gastric lymphomas (Tab. 1, Fig. 2, Ref. 13).

Is the dopamine D3 receptor mRNA on blood lymphocytes help to for identification and subtyping of schizophrenia?

Schizophrenia is one of the neuropathological disorders, which are associated with dopamine and its receptors. In recent years, it has been shown that mRNA of D3, D4 and D5 dopamine receptor (DRD3, DRD4, DRD5) subtypes is expressed in human peripheral blood lymphocytes (PBL). A total 55 schizophrenic patients and 51 healthy subjects were included in the study to investigate the levels of DRD3 mRNA in PBL of schizophrenic patients and whether DRD3 mRNA level in PBL can serve as peripheral marker for schizophrenia. RNA was isolated from lymphocytes of both groups and reverse transcriptase polymerase chain reaction (RT-PCR) was performed for DRD3 mRNA. We found a significant difference in PBL DRD3 mRNA levels among schizophrenia subtypes (P=0.030) while no difference was detected between control subjects and schizophrenics. We concluded that the levels of DRD3 mRNA can help understanding and severity of clinical manifestations in schizophrenia.

The effect of probiotics on prevention of upper respiratory tract infections in the paediatric community - a systematic review.

Prevention of acute upper respiratory tract infections (URTIs) is becoming an increasingly important concept in public health application due to the increase in antibiotic resistance. Probiotics have been shown to have some effect on prevention in various reviews. In this study we aimed to re-asses the effect of probiotics as there has been a substantial increase in literature regarding the effects and safety of probiotics in the paediatric population. Two major databases were systematically searched to identify clinical trials eligible for inclusion. Study selection, data extraction and quality assessment were carried out by two reviewers. This review comprises 33 randomised controlled trials (RCTs) applied to a paediatric population with high-quality methodology. The primary outcome for this review was the incidence of respiratory tract infections. Secondary outcomes were severity of symptoms, missed days of school, incidence of antibiotic use and safety of prebiotic use. This review showed that probiotics have an impact on decreasing the incidence of URTIs and the severity of symptoms. The use of probiotics is extremely safe and as studies increase in evaluation of the effect of probiotics more and more show a significant beneficiary effect. Although still a long way from becoming a unanimous treatment modality, the small positive changes that probiotics have on URTIs is important to consider and the use of probiotics should be encouraged more.

The overlooked association between lower urinary tract dysfunction and psychiatric disorders: a short screening test for clinical practice.

INTRODUCTION: Lower urinary tract dysfunction (LUTD) often presents with other associated comorbidities such as urinary tract infections, constipation, fecal incontinence, and vesicoureteral reflux. However, the psychiatric conditions that can be associated with LUTD tend to go unnoticed. The evaluation, diagnosis, and treatment of LUTD and psychiatric disorders in children are difficult and time-consuming. Moreover, there is currently no accepted consensus on this subject. OBJECTIVE: In this study, the authors aimed to investigate the relationship between the subgroups of both LUTD and psychiatric disorders. STUDY DESIGN: LUTD were divided into 4 groups by using voiding dysfunction symptom score (VDSS), bladder diary, and uroflowmetry/electromyography (UF/EMG) test. A short screening test for psychological problems was used to detect psychiatric disorders accompanying each LUTD group. In terms of psychiatric disorders, the patients were divided into two groups: externalizing and internalizing disorders. RESULTS: A total of 156 children were diagnosed with LUTD. Seventy-six patients had overactive bladder (OAB), 53 had dysfunctional voiding (DV), 14 had primary bladder neck dysfunction (PBND), and 13 had underactive bladder (UAB). Psychiatric disorder was detected in 46 children (29.4%). Of these, 32 had an externalizing and 14 had an internalizing disorder. In terms of age, externalizing disorders were more common in children aged between 6 and 11 years (87.5%), whereas internalizing disorders were seen equally in both age groups. Among these, attention deficit hyperactivity disorder (ADHD) was the most common psychiatric disorder (16.1%). The LUTD groups with the most frequent psychiatric disorders were UAB (53.8%), PBND (35.7%), and OAB (28.9%). DISCUSSION: Most of the studies investigating the relationship between the lower urinary tract and psychiatric disorders so far have been concerned with the lower urinary tract symptom (LUTS) (such as nighttime or daytime incontinence) and ADHD. However, the present study was performed according to the LUTD classification, which is primarily based on VDSS, bladder diary, and UF/EMG tests. Furthermore, psychiatric disorders were classified into their subgroups. The results have shown that around a quarter of children with LUTD also had comorbid psychiatric disorders. The relationship between LUTD and psychiatric disorders constitutes a critical point. Identifying this association can contribute to the comprehensive diagnosis and treatment for these patients. CONCLUSIONS: LUTD and psychiatric disorders can be seen together, and this can be detected by the short screening test for psychological problems. Therefore, the authors think that patients who applied with LUTS should undergo this short test along with the routine urinary system examination and tests.

Effects of penile fracture and its surgical treatment on psychosocial and sexual function.

The current therapy for penile fracture is immediate surgical repair, but sexual and psychosocial effects of the repair have been poorly investigated. We aimed to assess the impact of surgical correction of penile fracture on psychosocial status, sexual function, and erectile quality. Sixty-four patients classified into two subgroups according to follow-up: 2-24 months (Group 1), and longer than 24 months (Group 2), and 28 healthy men (Control group). The mean overall follow-up period was 39.1±32.7 months. The number of sexual intercourse origin was 44 (68.8%), the mean time interval from incident-to-surgery was 13.6±9.3 h. The mean sexual relationship score decreased during first year (P=0.001), and significant recovery was observed over 12-24 months. The mean overall relationship scores and the mean self-esteem scores of the study groups decreased until the end of the 24 months (P<0.05). The mean erectile function domains remained stable in all groups (P>0.05). The mean EHS scores were lower but the difference was not significant in the study groups (P>0.05). Penile fracture repair have no detrimental effect on sexual function, but psychogenic aspect may be adversely affected. This article concludes lower complication rates can be reached with immediate surgical correction of the penile fracture whereas psychogenic recovery might prolonged.

Gene expression profiling and analysis of signaling pathways involved in priming and differentiation of human neural stem cells.

Human neural stem cells have the ability to differentiate into all three major cell types in the CNS including neurons, astrocytes and oligodendrocytes. The multipotency of human neural stem cells shed a light on the possibility of using stem cells as a therapeutic tool for various neurological disorders including neurodegenerative diseases and neurotrauma that involve a loss of functional neurons. We have discovered previously a priming procedure to direct primarily cultured human neural stem cells to differentiate into almost pure neurons when grafted into adult CNS. However, the molecular mechanism underlying this phenomenon is still unknown. To unravel transcriptional changes of human neural stem cells upon priming, cDNA microarray was used to study temporal changes in human neural stem cell gene expression profile during priming and differentiation. As a result, transcriptional levels of 520 annotated genes were detected changed in at least at two time points during the priming process. In addition, transcription levels of more than 3000 hypothetical protein encoding genes and EST genes were modulated during the priming and differentiation processes of human neural stem cells. We further analyzed the named genes and grouped them into 14 functional categories. Of particular interest, key cell signal transduction pathways, including the G-protein-mediated signaling pathways (heterotrimeric and small monomeric GTPase pathways), the Wnt signaling pathway and the TGF-beta pathway, are modulated by the neural stem cell priming, suggesting important roles of these key signaling pathways in priming and differentiation of human neural stem cells.

Immunohistochemical study on distribution of endocrine cells in gastrointestinal tract of flower fish (Pseudophoxinus antalyae).

AIM: To detect distribution and relative frequency of endocrine cells in gastrointestinal tract of flower fish (Pseudophoxinus antalyae). METHODS: The intestinal tract of flower fish was divided into four portions from proximal to distal; the enlarged area after oesophagus and anterior, middle and posterior intestine. Immunohistochemical method using the peroxidase anti-peroxidase complex was employed. All antisera between four portions of flower fish were compared using ANOVA. RESULTS: Eleven types of gut endocrine cells were determined; they were immunoreactive for calcitonin gene related peptide, substance P, vasoactive intestinal peptide, bombesin, somatostatin-14, secretin, TrkA, TrkB, TrkC, neurotensin, neuropeptide Y, which were found in almost all portions of the gastrointestinal tract. CONCLUSION: The regional distribution and relative frequency of immunoreactive cells in the flower fish, Pseudophoxinus antalyae, are essentially similar to those of other fish.

Role of fibroblast growth factor receptor signaling in prostate cancer cell survival.

BACKGROUND: Expression of fibroblast growth factors (FGFs) is increased in a substantial fraction of human prostate cancers in vivo and in prostate cancer cell lines. Altered FGF signaling can potentially have a variety of effects, including stimulating cell proliferation and inhibiting cell death. To determine the biologic significance of altered FGF signaling in human prostate cancer, we disrupted signaling by expression of a dominant-negative (DN) FGF receptor in prostate cancer cell lines. METHODS: PC-3, LNCaP, and DU145 prostate cancer cells were stably transfected with DN FGFR constructs, and LNCaP and DU145 cells were infected with a recombinant adenovirus expressing DN FGFR-1. The effect of DN FGFR-1 expression was assessed by colony-formation assays, cell proliferation assays, flow cytometry, and cytogenetic analysis. Key regulators involved in the G(2)-to-M cell cycle transition were assessed by western blotting to examine cyclin B1 expression and by in vitro kinase assay to assess cdc2 kinase activity. RESULTS: Stable transfection of the DN FGFR-1 construct inhibited colony formation by more than 99% in all three cell lines. Infection of LNCaP and DU145 prostate cancer cells with adenovirus expressing DN FGFR-1 led to extensive cell death within 48 hours. Flow cytometry and cytogenetic analysis revealed that the DN FGFR-1 receptor led to arrest in the G(2) phase of the cell cycle before cell death. Cyclin B1 accumulated in DN FGFR-1-infected LNCaP cells, but cdc2 kinase activity was decreased. CONCLUSIONS: These findings reveal an unexpected dependence of prostate cancer cells on FGF receptor signal transduction to traverse the G(2)/M checkpoint. The mechanism for the G(2) arrest is not clear. Our results raise the possibility that FGF-signaling antagonists might enhance the cell death induced by other prostate cancer therapies.

The usefulness of left atrial volume index and left ventricular mass index in determining subclinical cardiac involvement in patients with early-stage sarcoidosis.

BACKGROUND AND AIM: Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. The present study has been designed to evaluate the importance of diastolic dysfunction with left atrial volume index (LAVi) and left ventricular mass index (LVMi) in determining subclinical cardiac involvement in subjects with stage I-II pulmonary sarcoidosis. METHODS: A total of 54 patients under follow-up for sarcoidosis without cardiac involvement and 56 healthy subjects were included in the study. The echocardiographic assessment of the patients revealed no significant difference between the two groups regarding left ventricular end-systolic and end-diastolic diameters, ejection fraction (LVEF) and annular velocity determined by tissue Doppler evaluation. RESULTS: The LVEF calculated was 61.8 ± 7.8 % in the sarcoidosis group versus 64.1 ± 2.7 % in the control group (p = 0.04). Left ventricular interventricular septum thickness, posterior wall thickness, and relative wall thickness were significantly higher in the sarcoidosis group compared to the control group (p < 0.001). The sarcoidosis group had higher LVM and LVMi values compared to the control group (145 ± 18.1 and 79 ± 14 g/m(2), 135 ± 27.7 and 74 ± 14.2 g/m(2); p = 0.020 and p = 0.021, respectively). Left atrial end-systolic volume and LAVi were higher in the sarcoidosis group (28.7 ± 18.5; 15.6 ± 10.2) compared to the control group (16.6 ± 10.9; 8.9 ± 5.5) with a statistically significant difference (p < 0.001). CONCLUSION: The present study indicates diastolic dysfunction and increased LVMi despite normal systolic function in patients with early-stage sarcoidosis without cardiac involvement. Also, the diastolic parameters were normal without showing any significant difference compared to the control group while there was a statistically significant increase in LAVi. This finding suggests that LAVi may be the earliest marker of diastolic dysfunction in patients with early-stage sarcoidosis without cardiac involvement.

Establishment of two human prostate cancer cell lines derived from a single bone metastasis.

Human prostate cancer cell lines are particularly difficult to establish, and most existing cell lines do not exhibit features commonly seen in human prostate cancer. Most available models either grow only in vivo as xenografts or are androgen insensitive and fail to express prostate-specific antigen (PSA). The lack of functionally relevant model systems of advanced prostate cancer has limited prostate cancer research and therapy development. Of 30 processed samples derived from patients with prostate cancer, we established two cell lines (MDA PCa 2a and MDA PCa 2b) that express PSA and androgen receptor, grow in vitro, and are androgen sensitive. Cells from these lines produced tumors in nude mice when injected either s. c. or orthotopically (intraprostatic). Both cell lines were established from a bone metastasis of a patient whose cancer was exhibiting androgen-independent growth. Although both were derived from two samples of the same specimen, they have different genetic features (as assessed by karyotype analysis) and different phenotypes (e.g., morphology and growth rate). It is likely that they are distinct clones isolated by the use of different culture procedures and reflect the genetic heterogeneity of the tumor. These new cell lines are the first available derived from a bone metastasis of an androgen-independent prostatic adenocarcinoma that grow both in vivo and in vitro and have retained PSA expression and androgen sensitivity. They therefore constitute important model systems to address critical questions related to the androgen-independent growth of human prostate cancer and to the complex process of bone metastasis.

The history of probiotics: the untold story.

Probiotic, a word derived from Latin, means 'for life'. A long time before the awareness of probiotic microorganisms, fermented products, such as beer, bread, wine, kefir, kumis and cheese had been very frequently used for nutritional and therapeutic purposes. It is widely believed that fermented products were probably found, or better to say, discovered spontaneously. The legend tells that yoghurt is most likely resulted from a fermentation process within the animal skin bags used for transportation of water and milk in regions with low humidity and high temperatures (Middle Asia and Middle East). The history of probiotics goes paralel with the evolution of human race and, thanks to the sophisticated techniques at the moment, can be traced back to the ancient times, nearly 10,000 years ago. The aims of this review are to highlight the important events for probiotic history, to correct the widely available anonymous misinformation in the literature and to remind to the readers important characters in its history.

Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.

Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.

Caspase-dependent apoptosis induced by telomere cleavage and TRF2 loss.

Chromosomal abnormalities involving telomeric associations (TAs) often precede replicative senescence and abnormal chromosome configurations. We report here that telomere cleavage following exposure to proapoptotic agents is an early event in apoptosis. Exposure of human and murine cancer cells to a variety of pro-apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, and cancer chemotherapeutic agents) resulted in telomere cleavage and aggregation, and finally their extrusion from the nuclei. Telomere loss was associated with arrest of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and subsequent large-scale chromatin cleavage were inhibited by overexpression of the anti-apoptotic protein, bcl-2, and two peptide caspase inhibitors (BACMK and zVADfmk), indicating that both events are regulated by caspase activation. The results demonstrate that telomere cleavage is an early chromatin alteration detected in various cancer cell lines leading to drug-induced apoptosis, and suggest that this event contributes to mitotic catastrophe and induction of cell death. Results also suggest that the decrease of telomeric-repeat binding factor 2 (TRF2) may be the earliest event in the ara-C-induced telomere shortening, induction of endoreduplication and chromosomal fragmentation leading to cell death.

The role of fibroblast growth factors and their receptors in prostate cancer.

Prostate cancer is the most common malignancy in men in the USA and the second leading cause of cancer deaths. Fibroblast growth factors (FGFs), including FGF1 (acidic FGF), FGF2 (basic FGF), FGF6 and FGF8 are all expressed at increased levels in prostate cancer as paracrine and/or autocrine growth factors for the prostate cancer cells. In addition, increased mobilization of FGFs from the extracellular matrix in cancer tissues can increase the availability of FGFs to cancer cells. Prostate cancer epithelial cells express all four types of FGF receptors (FGFR-1 to -4) at variable frequencies. Expression of FGFR-1 and FGFR-4 is most closely linked to prostate cancer progression, while the role of FGFR-2 remains controversial. Activation of FGF receptors can activate multiple signal transduction pathways including the phospholipase Cgamma, phosphatidyl inositol 3-kinase, mitogen-activated protein kinase and signal transducers and activators of transcription (STAT) pathways, all of which play a role in prostate cancer progression. Sprouty proteins can negatively regulate FGF signal transduction, potentially limiting the impact of FGF signaling in prostate cancer, but in a significant fraction of prostate cancers there is decreased expression of Sprouty1 mRNA and protein. The effects of increased FGF receptor signaling are wide ranging and involve both the cancer cells and surrounding stroma, including the vasculature. The net result of increased FGF signaling includes enhanced proliferation, resistance to cell death, increased motility and invasiveness, increased angiogenesis, enhanced metastasis, resistance to chemotherapy and radiation and androgen independence, all of which can enhance tumor progression and clinical aggressiveness. For this reason, the FGF signaling system it is an attractive therapeutic target, particularly since therapies targeting FGF receptors and/or FGF signaling can affect both the tumor cells directly and tumor angiogenesis. A number of approaches that could target FGF receptors and/or FGF receptor signaling in prostate cancer are currently being developed.

Ag-NOR studies in a human lymphocyte culture: are variants localized to specific chromosomes?

The genomic activity and polymorphisms of nucleolus organizer regions (NORs) were studied in an individual with routinely used AgNO3 and Q-banding techniques. The results demonstrate that (a) the mean number of NORs per metaphase spread was 7.4, (b) chromosomes 14, 13, 15, and 21 showed variations of Ag-NOR in decreasing order, (c) chromosome 22 did not show a polymorphism in any cell examined, and (d) both chromosomes 14 showed silver staining in most cells. Unlike many earlier reports indicating that NOR variants were constitutional in each individual, our present case represented a mosaic pattern of polymorphism involving most of the D- and G-group chromosomes.

Establishment of an in vitro cell model system to study human prostate carcinogenesis.

A positive family history of prostate cancer is a risk factor for this disease, suggesting that alterations of certain genes may play an important role in the development and progression of prostate cancer. However, genetic alterations responsible for initiation and acquisition of metastatic phenotypes by prostate cancer are not well defined. We have observed a consistent change in chromosome 5 in an in vitro cell model of human prostate carcinogenesis in which the near-diploid cells from the surrounding tissue of an adenocarcinoma of the prostate obtained from a 42-year-old patient were subjected to in vitro cell culture and passages. We have examined three different passages of this cell strain by conventional and molecular cytogenetic methods and have seen an increased number of alterations in chromosome 5 in higher passage cells, with accompanying changes in cell morphology. In late passages of this cell line, no cell showed two normal copies of chromosome 5 as analyzed by G-banding and fluorecent in situ hybridization (FISH). The long arm (q) of chromosome 5 was either missing or involved in structural rearrangements. This observation suggests that the q arm of chromosome 5 may carry a tumor suppressor gene(s) that is well-expressed in normal prostate tissue, but when one of these tumor suppressor gene(s) is mutated or deleted and its encoded mRNA and protein are differentially expressed or not expressed at all in the prostate cells, then it may lead to initiation of tumor growth and development. Cytogenetic analyses of early passage cells in this cell strain revealed that approximately 78.8% of metaphases were normal, with a 46,XY chromosome constitution, and 21.2% of cells had clonal alterations mostly of chromosomes 5, 7, 8, 15, 16 and Y. In the middle passages, abnormal cells increased in number (78.26%) and also showed a large number of chromosomal changes. In the late passages, all cells showed structural and numerical abnormalities of the same chromosomes, in addition to some new markers; no cells were found to have a normal karyotype. These chromosomal aberrations could be considered early markers of prostate carcinogenesis. Some of the markers present in late passage cells were similar to those reported in a well-characterized prostate cancer cell line, LNCaP.