A case of transitional cell carcinoma of the bladder with a del(9)(q11q21.2)

Monosomy for chromosome 9, as well as loss of heterozygosity for markers on this chromosome, has been detected in a high percentage of transitional cell carcinomas (TCC) of the bladder. We report a case of a TCC of the bladder with an interstitial del(9)(q11q21.2) that could be indicative of the presence of a putative tumor-suppressor gene related to bladder tumor progression. To elucidate the role of chromosome 9 in bladder tumors, it would be interesting to study a possible loss of heterozygosity in this chromosome region.     

A recurrent nonrandom translocation (3;7)(q27;p12) associated with BCL-6 gene rearrangement in B-cell diffuse large cell lymphoma

BACKGROUND: To overcome the relatively low accuracy of exercise stress testing (EST) in detecting coronary artery disease (CAD), both echocardiography and perfusion scintigraphy have been evaluated in conjunction with pharmacologic stress, but there is still uncertainty of the relative value of these tests as possible first-line examinations for suspected CAD. This study evaluated the accuracy of EST, dipyridamole and dobutamine stress echocardiography (DIP-ECHO, DOB-ECHO), and dipyridamole and dobutamine technetium 99m sestamibi tomography (DIP-MIBI, DOB-MIBI) for the detection of CAD in patients evaluated for the first time because of chest pain. METHODS AND RESULTS: Sixty patients underwent EST, DIP-ECHO, DOB-ECHO, DIP-MIBI, and DOB-MIBI. Echocardiographic images were acquired simultaneously with sestamibi injections, and the scintigraphic images were collected 1 hour later. Coronary angiography was performed within 15 days. Out of 33 patients with significant (>70%) coronary stenoses, 19 (58%) were correctly identified by EST, 18 (55%) by DIP-ECHO, 20 (61%) by DOB-ECHO, 32 (97%) by DIP-MIBI, and 30 (91%) by DOB-MIBI (p < 0.005 for MIBI vs EST and ECHO). The specificity of EST was 67% (p < 0.05 vs ECHO and MIBI), 96%, 96%, 89%, and 81%, respectively. Of the 62 stenotic coronary arteries, 20 (32%) were correctly identified by DIP-ECHO, 24 (39%) by DOB-ECHO, 48 (77%) by DIP-MIBI, and 45 (73%) by DOB-MIBI. The sensitivity of the imaging techniques in predicting the presence of multivessel disease was 14% and 29% for DIP and DOB-ECHO compared with 48% and 57% for DIP and DOB-MIBI. CONCLUSIONS: Our results confirm the limited reliability of EST in detecting CAD and the good diagnostic value of DIP and DOB-MIBI. Conversely, the lower sensitivity and the poorer capability to recognize multivessel CAD do not support the role of either DIP or DOB-ECHO as first-line examination for suspected CAD.     

Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier

PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine antagonist prochlorperazine to the combination of granisetron and dexamethasone in the prevention of acute nausea and vomiting following high-dose cisplatin. PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2) (median dose = 100 mg/m2) were enrolled at three sites. Patients received prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and 10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10 micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed during the 24-hour period after cisplatin using complete antiemetic response (no emetic episodes and no rescue antiemetics) and patient assessment of nausea and satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of patients. Forty-two patients (72%) experienced no nausea. The mean change in posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight patients (83%) were completely satisfied with their antiemetic treatment. The mean posttreatment patient satisfaction score was 92 mm. Treatment was well tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug antiemetic regimen is well tolerated and highly effective in the prevention of acute nausea and vomiting arising from high-dose cisplatin. Further studies evaluating this regimen are warranted.     

Molecular analysis to assign parental origin and distinguish de novo i(21q) from t(21q21q) in two Down syndrome fetuses

OBJECTIVE: We sought to determine the origin of two prenatal cases of chromosome 21 rearrangements not amenable to clarification by conventional cytogenetic methodology. METHODS: Hypervariable repeat polymorphisms (chromosome 21) were used to determine the type of structural rearrangement and the parental origin of the rearranged chromosome. The repeats used were highly polymorphic and located very close to the centromere; thus, the likelihood of differences among the parental alleles and overall informativeness were increased. RESULTS: The rea(21q21q) chromosomes were identified as a Robertsonian translocation in one fetus and an isochromosome in the other. The extra chromosome material was found to be maternal in origin in both cases. CONCLUSION: The ability to clarify the origin of abnormal chromosomal rearrangements provides valuable information concerning possible mechanisms of aneuploidy, as well as clinical data that may have an impact in assessing a patient's risk for abnormal offspring.     

Intraepithelial carcinoma of the cervix uteri. 1) Cytologic detection in gynecologic practice. Our exerience with 15,000 smears

The best results in screening for subclinical cancer of the cervix are given by cytological studies. The authors in reviewing their experience in this method of screening studied the result of 15,000 smears which gave a diagnosis of 37 cases of intra-epithelial carcinoma of the cervix, which means 1 case of carcinoma in situ diagnosed in every 400 smears. Although the technique is very simple it has to be carried out according to strict criteria at the time of taking the smear, of fixing it immediately and of staining it. There is a group of patients who are at high risk about the age of forty, when there is a marked influence due to parity. But only a systematic policy will bring about diagnosis of pre-invasive carcinoma in cases where the cervix is clinically healthy. The cytology is usually characteristic, though the diagnosis may be difficult during pregnancy, or when hormone contraception is being used or when there is a trichomonas infection present. This explains why we find false positives in 0.03 per cent of cases in this study and false negatives in 0.03 per cent of cases. Their rarity means that the method is 99.94 per cent reliable. Finally, the cervical smear gives an opportunity for studying the vaginal microbial flora as well as the cyto-hormonal state.     

A new translocation involving chromosomes no. 5 and no. 12 t(5;12) (5q15;12p13)

A new case of translocation between chromosomes No. 5 and No. 12 is described. The translocation t(5;12) (5q15;12p13) is apparently balanced and was found in a child aged 3 1/2 years who was affected with severe psychomotor retardation. On the basis of the clinical picture it is suggested that the phenotype could be not dependent on the chromosomal alteration.     

Loss of p16 gene in bladder cancer and genitourinary carcinoma cell lines

To determine whether p16, a novel antioncogene, is altered in human bladder cancer and urogenital carcinoma cell lines, we examined a series of 10 primary bladder cancer and 4 urogenital carcinoma cell lines (BIU-87, EJ, GRC and PC-3M) by southern blot. Two cases of 10 primary bladder cancer and EJ, BIU-87 PC-3M had homozygous deletion of p16, and 2 cases of 10 primary bladder cancer had loss of heterozygous. Loss of p16 may provide an additional growth advantage and carcinogenesis.     

Clinical relevance of the i(12p) marker chromosome in germ cell tumors

BACKGROUND: Germ cell tumors in men are curable at all stages and are among the most sensitive of all cancers to chemotherapy. An isochromosome of the short arm of chromosome 12, i(12p), has been reported to be a frequent marker of these tumors and to have diagnostic and prognostic significance. PURPOSE: We evaluated the possible association between this cytogenetic marker and clinical outcome for men with germ cell tumors. METHODS: One hundred seventy-eight germ cell tumor samples from 150 men were studied using conventional and molecular cytogenetic techniques. Of these samples, 171 were evaluable. Patient characteristics, disease stage, treatment outcome, and disease status were correlated with the observed cytogenetic changes. In addition, 28 biopsy specimens obtained from 28 patients with tumors of uncertain histogenesis were evaluated to determine whether the presence of i(12p) could serve as a diagnostic marker of a germ cell origin for these tumors. RESULTS: Of the 171 evaluable tumor accessions, 101 (59%) yielded abnormal karyotypes. i(12p) was determined to be present in 79 of the 101 (79%) abnormal karyotypes, which were derived from all cell types and primary sites. An abnormal karyotype was more frequently obtained from nonseminomatous tumors (91/137 [81%]) than from seminomas (10/34 [30%] [P < .001]). Tumors resulting in a cytogenetic failure were more likely to respond completely to chemotherapy than tumors with an abnormal karyotype (P = .004). i(12)p copy number was not associated with response or survival. Fluorescence in situ hybridization using a chromosome 12 centromere-specific probe detected i(12p) in 47 of 47 tumors (100%) already shown to have i(12p) by cytogenetic analysis and in 13 of 49 tumors (27%) exhibiting either an abnormal karyotype or a cytogenetic failure. One or more copies of i(12p), excess 12p copy number, or a deletion on the long arm of chromosome 12 was found in seven of 28 (25%) midline tumors of uncertain histogenesis, thus establishing a diagnosis of a germ cell tumor in these patients. One partial and five complete responses were observed in these seven patients. Only two partial responses were seen in the 17 patients who had no detectable germ cell tumor-related cytogenetic marker (P = .009). CONCLUSIONS: i(12p) is a highly nonrandom chromosomal marker seen in about 80% of male germ cell tumors with evaluable cytogenetic abnormalities. The presence of this isochromosome has diagnostic and possibly prognostic importance for patients with these tumors. IMPLICATIONS: Cytogenetic studies of germ cell tumors in prospective clinical treatment trials are warranted to define more precisely the relationship between histologic subtype, serum tumor marker production, and prognosis.     

Chromosome bands 3p14.2, 9p21, and 13q14 are frequently deleted in roentgenographically occult bronchogenic squamous cell carcinoma of the lung

This study was undertaken to determine whether melatonin (N-acetyl-5 methoxytryptamine) is effective in helping emergency medical services (EMS) personnel who work rotating night shifts reset their biological clocks and minimize circadian rhythm disruption. A double-blinded, randomized, crossover study was performed using 22 volunteers. Participants were working a span of consecutive night (2300 to 0700 hours) shifts and received either a melatonin capsule (6 mg) or placebo to be taken before each of the consecutive day sleeps. Each participant completed a total of 4 spans of consecutive night shifts (2 melatonin, 2 placebo). Collected data included daily sleep diaries, quantification of alcohol/caffeine consumed, and drug side effects. Assessment of sleep quality, posttreatment mood, and workload ratings were measured daily by 10-cm visual analog scale (VAS). Analysis of sleep diaries found no significant difference (P > .05) between the two treatments with respect to mean sleep latency, duration, and efficiency, and subjectively rated sleep quality. Similarly, no significant benefits were noted between the median VAS scores for daily posttreatment mood or workload ratings. Adverse effects were rare; one patient taking melatonin reported a prolonged sedative effect. Despite recent interest in melatonin for treatment of circadian-based sleep disorders, no clinical benefits were noted in EMS personnel working rotating night shifts.     

A newly developed adenovirus-mediated transfer of a wild-type p53 gene increases sensitivity to cis-diamminedichloroplatinum (II) in p53-deleted ovarian cancer cells

A new recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) was developed and the combination effect of p53 gene transfer and cis-diamminedichloroplatinum (II) (CDDP) was examined in an ovarian cancer cell line, SK-OV-3, with deletion of the p53 gene. AxCAp53 showed a high efficiency of gene transduction and increased sensitivity to CDDP in the SK-OV-3 cells. It was found that the sensitivity of the cells to CDDP correlated with the amount of infectious units of virus per cell of AxCAp53 which correlated with p53 protein expression. The results suggest that the combination of CDDP and AxCAp53 may be a potential strategy for the therapy of CDDP-resistant ovarian cancer.     

Elliptocytosis in myelodysplastic syndrome associated with translocation (1;5)(p10;q10) and deletion of 20q

OBJECTIVE: To assess the efficacy of prolonged high pressure angioplasty for dilatation of calcified and stenotic cardiac conduits in children. DESIGN: A prospective study of consecutive patients presenting with calcified and stenotic conduits. SETTING: Two tertiary paediatric cardiology departments. METHODS: Sustained (up to five minutes), high pressure (up to 18 atmospheres), double balloon angioplasty was performed in six calcified and stenotic cardiac conduits (five consecutive patients, three male, two female, age 4 to 17 years). Four patients had right ventricle to pulmonary artery (RV-PA) conduits, and one had two venous conduits in a Fontan circulation. RESULTS: Marked reductions in right ventricle to pulmonary artery gradients, from a median (range) of 48 (40 to 62) mm Hg to 11 (5 to 16) mm Hg, and in right ventricle to femoral artery pressure ratios, from a median of 0.8 (0.72 to 0.86) to 0.4 (0.33 to 0.44), were achieved for all RV-PA conduits. All five patients had sustained clinical improvement at follow up (median follow up 12 months) and none has required reintervention or surgery. CONCLUSIONS: Prolonged high pressure double balloon angioplasty may have a role in prolonging the interval between conduit replacements in a subset of patients with complex heart defects.     

A group of deltanoids (vitamin D analogs) regulate cell growth and proliferation in small cell carcinoma cell lines

A group of deltanoids has been used for studying the inhibition of cell growth and proliferation in two small cell lung carcinoma (SCLC) in vitro. The biologically active deltanoid, 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3), has functions beyond its classical roles of stimulating calcium transport and serum calcium. It also causes the differentiation of a variety of precursor cells and suppresses growth. Although 1,25(OH)2D3 has an inhibitory effect on growth of certain malignant cells, its hypercalcemic effect has prevented clinical applications. Several new deltanoids, which showed comparable or even greater abilities to induce differentiation and to inhibit proliferation, have been identified. Furthermore, these synthetic deltanoids have been shown to be less effective on calcium metabolism and less hypercalcemic. We have selected four synthetic deltanoids; MC-903, 1 alpha-OH-pregnacalciferol, 19-nor-24 homo, and 19-nor-22(E). When compared with 1,25 (OH)2D3, these deltanoids showed considerable potency on cell growth and proliferation in the NCI-H82 and the NCI-H209 SCLC lines. Cells were treated with various concentrations of deltanoids. They inhibited the growth and proliferation of both SCLC cells in vitro in a time-and dose-dependent manner, as determined by cell number and 3H-thymidine uptake. 19-nor-22(E) showed an antiproliferative effect significantly comparable to 1,25(OH)2D3 in the NCI-H82 cell line 1 alpha-OH-pregnacalciferol, 19-nor-24 homo, and 19-nor-22(E) inhibited the cell growth in the NCI-H209 cells within the same significance as 1,25 (OH)2D3. The degree of the suppressive effect of the deltanoids was cell line dependent.     

Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23)

We describe two new human leukemia cell lines, MOLM-13 and MOLM-14, established from the peripheral blood of a patient at relapse of acute monocytic leukemia, FAB M5a, which had evolved from myelodysplastic syndrome (MDS). Both cell lines express monocyte-specific esterase (MSE) and MLL-AF9 fusion mRNA. Gene fusion is associated with a minute chromosomal insertion, ins(11;9)(q23;p22p23). MOLM-13 and MOLM-14 are the first cell lines with, and represent the third reported case of, MLL gene rearrangement arising via chromosomal insertion. Both cell lines carry trisomy 8 which was also present during the MDS phase, as well as the most frequent trisomies associated with t(9;11), ie, +6, +13, +19 variously present in different subclones. Despite having these features in common, differences in antigen expression were noted between the two cell lines: that of MOLM-13 being CD34+, CD13-, CD14-, CD15+, CD33+; whereas MOLM-14 was CD4+, CD13+, CD14+, CD15+, CD33+. Differentiation to macrophage-like morphology could be induced in both cell lines after stimulation with INF-gamma alone, or in combination with TNF-alpha, which treatment also induced or upregulated, expression of certain myelomonocyte-associated antigens, including CD13, CD14, CD15, CD64, CD65 and CD87. Together, these data confirm that both cell lines are likely to be novel in vitro models for studying monocytic differentiation and leukemogenesis.     

A new non-random chromosomal translocation t(3;6)(q27;p21.3) associated with BCL6 rearrangement in two patients with non-Hodgkin's lymphoma

We describe two cases of non-Hodgkin's lymphoma associated with t(3;6)(q27;p21.3) and BCL6 rearrangement. The first case was in a 78-year old woman, whose performance status (PS) was 1, the serum lactate dehydrogenase (LDH) level was elevated, and the Ann Arbor stage was IIIA with no extra nodal lymphomatous site. The pathological diagnosis from a biopsy of the inguinal lymph node was 'malignant lymphoma (ML), follicular, small cleaved' according to the Working Formulation. Complete remission was achieved. Although she had relapse in 1992, remission was obtained again. The second case was in a 62-year old man, whose PS was 1, the serum LDH was normal, and Ann Arbor stage was IVA with the involvement of the small intestine. Histological diagnosis of the cervical lymph node was 'ML, diffuse, large cell'. Complete remission was obtained without relapse. The 3q27 translocations, found in 20-30% of non-Hodgkin's lymphoma, are unique in having multiple chromosomal translocation partners. Chromosome band 6p21.3 is one of these partner sites that may be the site of a novel gene. The two cases presented here show that this translocation is a non-random chromosomal change involving 3q27 and BCL6. Since t(3;6) was the sole karyotypic abnormality in one case, this translocation may play a role in lymphomagenesis.