TY - JOUR AB - Heat shock proteins (HSPs) play important roles in tumor immunity. The authors prospectively investigated the correlation between the tumor-specific Hsp70 membrane expression as an independent clinicopathological marker and overall survival in tumor entities that differ in their route of metastasis. METHODS: Hsp70 membrane expression was examined by flow cytometry in 58 colon, 19 gastric, 54 lower rectal carcinoma, and 19 squamous cell carcinoma specimens and the corresponding normal tissues at time of first diagnosis. Kaplan-Meier survival curves were analyzed to determine the relation of Hsp70 expression to the patients' prognosis. RESULTS: An Hsp70 membrane-positive phenotype was found in 40% (colon), 37% (gastric), 43% (lower rectal), and 42% (squamous cell) of the analyzed tumor specimens. None of the corresponding normal tissues was found to be Hsp70 membrane-positive. In patients with colon (P = .032) and gastric (P = .045) carcinomas, an Hsp70 membrane expression correlated significantly with an improved overall survival; a negative association was seen in lower rectal (P = .085) and squamous cell carcinoma (P = .048). CONCLUSIONS: The authors hypothesized that differing relations between surface expression of Hsp70 on tumor cells and clinical outcomes may reflect differences in the route of metastases. Colon and gastric carcinomas metastasize into the liver where hepatic natural killer cells may have the capacity to recognize and kill Hsp70 membrane-positive tumor cells and thus account for a better overall survival. AU - Pfister, K.* AU - Radons, J.* AU - Busch, R.* AU - Tidball, J.G.* AU - Pfeifer, M.* AU - Freitag, L.* AU - Feldmann, H.J.* AU - Milani, V. AU - Issels, R.D. AU - Multhoff, G. C1 - 2063 C2 - 24693 SP - 926-935 TI - Patient survival by Hsp70 membrane phenotype: Association with different routes of metastasis. JO - Cancer Cytopathol. VL - 110 IS - 4 PB - Wiley-Blackwell PY - 2007 SN - 1934-662X ER - TY - JOUR AU - Gellermann, J.* AU - Hildebrandt, B.* AU - Issels, R.D. AU - Ganter, H.* AU - Wlodarczyk, W.* AU - Budach, W.* AU - Felix, R.* AU - Tunn, P.-U.* AU - Reichardt, P.* AU - Wust, P.* C1 - 5582 C2 - 23919 SP - 1373-1382 TI - Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia: Correlation with response and direct thermometry. JO - Cancer Cytopathol. VL - 107 PY - 2006 SN - 1934-662X ER - TY - JOUR AB - Papillomavirus is the etiologic agent associated with cervical carcinoma. The papilloma E2 protein is able to regulate negatively the expression of E6 and E7 papilloma oncoproteins. Therefore, a new, highly attenuated vaccinia virus known as modified vaccinia virus Ankara (MVA), which carries the papillomavirus E2 gene, was used for the treatment of tumors associated with human papillomavirus. Analysis of expression of the E2 gene from the recombinant vaccinia virus was performed by reverse transcription-polymerase chain reaction of RNA isolated from infected cells. Detection of the E2 protein was done by immunoprecipitation from proteins labeled with [(35)S]-methionine, isolated from infected cells. The therapeutic effect of the MVA E2 recombinant virus over human tumors was tested in nude mice bearing tumors generated by inoculation of HeLa cells. Series of 10 nude mice with tumors of different sizes were injected with MVA, MVA E2, or phosphate-buffered saline. Tumor size was monitored every week to assess growth. The MVA E2 recombinant virus efficiently expressed the E2 protein in BS-C-1 cells. This protein was able to repress, in vivo, the papillomavirus P105 promoter, which controls the expression of the E6 and E7 oncoproteins. In nude mice the MVA E2 virus reduced tumor growth very efficiently. In contrast, tumors continued to grow in mice treated with MVA or PBS. The life expectancy of MVA E2-treated mice was also increased three- to fourfold compared with that of animals that received MVA or PBS. The growth of human tumors was efficiently inhibited by the MVA E2 recombinant vaccinia virus. The absence of side effects in treated animals suggested that the MVA E2 virus is a safe biologic agent that could in the future be used in humans for the treatment of cervical carcinoma. AU - Graham, V.V.* AU - Sutter, G. AU - Jose, M.V.* AU - Garcia-Carranca, A.* AU - Erfle, V. AU - Mendoza, N.M.* AU - Merchant, H.* AU - Rosales, R.* C1 - 21387 C2 - 19504 SP - 1650-1662 TI - Human Tumor Growth is Inhibited by a Vaccinia Virus Carrying the E2 Gene of Bovine Papillomavirus. JO - Cancer Cytopathol. VL - 88 IS - 7 PY - 2000 SN - 1934-662X ER - TY - JOUR AB - BACKGROUND: This study evaluates the histopathology of lung carcinoma in relation to underground radon exposure. METHODS: Two hundred forty uranium miners of the former Wismut Company in Eastern Germany with histologically or cytologically confirmed primary lung carcinoma were recruited from 3 study clinics between 1991 and 1995. Information on smoking history was obtained by personal interviews, whereas job histories were derived from original payrolls provided by the Wismut Company. Quantitative estimates of occupational radon exposure were based on a job-exposure matrix. RESULTS: Squamous cell carcinoma (SqCC) was the predominant cell type (43%), followed by adenocarcinoma (AC; 26%), small cell lung carcinoma (SCLC; 23%), and other cell types (8%). Nearly all patients were smokers. Time since first occupational exposure was 42 years on average, the mean cumulative radon exposure 506 working level months. Adenocarcinoma appeared to be more likely than both SCLC and SqCC among miners with low cumulative radiation exposure, long time since first exposure, an older age at diagnosis, and among ex- and never-smokers. In current smokers, lung carcinomas developed at a much lower level of radiation exposure than in ex- and never-smokers. The increase in the relative frequency of SCLC and SqCC at the expense of AC with increasing cumulative radiation exposure was more pronounced among ex- and never-smokers and seemed to be masked among current smokers. CONCLUSION: The authors' data suggest that all cell types were associated with radon exposure, but high radiation exposure tended to increase the proportion of SCLC and SqCC. AU - Kreuzer, M. AU - Müller, K.M.* AU - Brachner, A. AU - Gerken, M. AU - Grosche, B. AU - Wiethege, T.* AU - Wichmann, H.-E. C1 - 21645 C2 - 19793 SP - 2613-2621 TI - Histopathologic Findings of Lung Carcinoma in German Uranium Miners. JO - Cancer Cytopathol. VL - 89 IS - 12 PY - 2000 SN - 1934-662X ER - TY - JOUR AB - BACKGROUND Previous research has demonstrated that adenocarcinoma is the leading cell type among patients with early age onset lung carcinoma. An increase in adenocarcinoma at the expense of squamous cell carcinoma in general was observed in recent years and may be due to the smoking of filtered cigarettes. METHODS To rule out whether shifts in smoking patterns or other etiologic factors are responsible for the high rates of adenocarcinoma in young patients, personal interviews regarding smoking, occupation, and family history of cancer were conducted in 251 young patients (age ≤ 45 years) and 2009 older patients (ages 55–69 years) with histologically confirmed lung carcinoma from selected study clinics in Germany between 1990 and 1996. RESULTS Young male patients were found to have significantly more adenocarcinomas (41%) than older male patients (28%), whereas adenocarcinomas were dominant in young and older women (43% and 47%, respectively). Because smoking patterns were different between young and older patients, the authors stratified for comparable levels of smoking exposure. Histology did not differ in never smokers (dominance of adenocarcinomas in both age groups) and in male heavy smokers (dominance of squamous cell carcinomas in both age groups), whereas young male low dose smokers showed significantly more cases of adenocarcinoma than older low dose smokers. A family history of lung carcinoma was significantly higher in young patients compared with older patients, but no association with histologic type was observed. CONCLUSIONS The results of the current study show that differences in the histologic type of lung carcinoma based on age at onset can be explained in part by differences in smoking patterns. However, there still are unknown factors that appear to favor the development of adenocarcinoma in the young. Cancer 1999;85:1958–65. © 1999 American Cancer Society. Carcinoma of the lung occurs most commonly in the sixth and seventh decades of life and is rarely found in young patients. Most studies over the past decades reported adenocarcinoma as the most frequent cell subtype among patients with early onset lung carcinoma of both genders,1–12 which is in contrast to squamous cell carcinoma as the most frequent type in older men.13 The predominance of adenocarcinoma in the young could reflect either a propensity of young individuals to develop this subtype or an increase in this subtype in recent years, which initially is reflected in younger cohorts. Some studies suggest that the reduction of tar yield and the introduction of filtered cigarettes in the 1960s could have favored the development of adenocarcinoma at the expense of squamous cell carcinoma.14, 15 Such shifts in the incidences of different histologic types of lung carcinoma have been found in the United States, where adenocarcinoma had become the most frequent subtype at the beginning of the 1980s.16–18 In Europe, squamous cell carcinoma still predominates in most countries. Levi and colleagues19 reported a remarkable rise in adenocarcinoma incidence in men and women from Switzerland, with rates of adenocarcinoma incidence among young adults in the early 1990s being more than three times higher than rates of squamous cell carcinoma. Up to now, it is still inconclusive whether or not high rates of adenocarcinoma in young subjects are mainly attributable to shifts in smoking pattern or whether other still unknown factors are causal. In a previous analysis of a case–control study of lung carcinoma, we found smoking and a possible genetic predisposition as risk factors for lung carcinoma in young subjects (≤45 years).20 In addition, a high percentage of adenocarcinomas in this young group compared with older patients (55–69 years) was observed. The aim of the present analysis of these data is to further investigate the association between histologic type and age of onset of lung carcinoma. This study provides a large number of young and older lung carcinoma patients of both genders, a detailed quantification of life-long smoking and occupational exposure, and information on family history of cancer.   AU - Kreuzer, M. AU - Kreienbrock, L. AU - Müller, K.M.* AU - Gerken, M. AU - Wichmann, H.-E. C1 - 20908 C2 - 18953 SP - 1958-1965 TI - Histologic Types of Lung Carcinoma and Age at Onset. JO - Cancer Cytopathol. VL - 85 IS - 9 PY - 1999 SN - 1934-662X ER - TY - JOUR AB - BACKGROUND: It has been established that comparative genomic hybridization (CGH) on Papanicolaou-stained cervical smears can be used to identify chromosomal imbalances. METHODS: In this study, the authors identified normal and dysplastic squamous epithelial cells cytologically, eliminated surrounding bacteria or leukocytes by a ultraviolet laser microbeam under microscopic control, and scraped out the cell groups of interest by a microdissection system. In 3 cases of squamous intraepithelial lesions (SIL), a total of 9 samples of dysplastic (n = 6) and nontumorous cells (n = 3) were investigated, each of them consisting of 3-40 cells. The DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and used for CGH. RESULTS: Analyses of all nontumorous cell groups resulted in fluorescence ratio profiles that showed no deviation from the normal range, confirming that no methodologic artefacts have been produced. The CGH profiles from dysplastic cells, however, showed various chromosomal imbalances affecting six to nine different chromosomes. The most frequent gains in DNA were observed on chromosomes 1p, 2q, 4, and 5, whereas losses were found on chromosomes 6q and 13q. CONCLUSIONS: The results of this study demonstrate the feasibility and reliability of CGH on microdissected cell samples of routinely processed cervical smears. To the authors' knowledge, this is the first study reporting the use of CGH on cervical routine smears. This approach offers the opportunity to investigate sequence copy number changes in small, morphologically well-defined groups of dysplastic cells. It may, therefore, serve as a cytogenetic screening test for identifying chromosomal aberrations in precancerous lesions that are associated with a high risk for progression to invasive cancer.   AU - Aubele, M. AU - Zitzelsberger, H. AU - Schenck, U.* AU - Walch, A.K. AU - Höfler, H. AU - Werner, M.* C1 - 20778 C2 - 18827 SP - 375-379 TI - Distinct cytogenetic alterations in squamous intraepithelial lesions of the cervix revealed by laser-assisted microdissection and comparative genomic hybridization. JO - Cancer Cytopathol. VL - 84 IS - 6 PY - 1998 SN - 1934-662X ER -