bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of human papillomavirus types 16 and 18 in squamous‐cell carcinoma of the penis: A retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction
Authors: Wiener John S. , Effert Peter J. , Humphrey Peter A. , Yu Li , Liu Edison T. , Walther Philip J.
Published: February 2007

Human papillomaviruses (HPV), particularly types 16 and 18, may be carcinogenic effectors in a variety of human lower‐genital‐tract malignancies. Using the highly sensitive technique of differential polymerase chain reaction (D‐PCR) with amplimers from the E6 open reading frames of HPV types 16 and 18, a retrospective analysis of a 20‐year institutional experience with squamous‐cell carcinoma of the penis (SCCP) was performed to determine the prevalence of these HPV types in this malignancy. Paraffin‐embedded surgical specimens of primary (N = 27), locally recurrent (N = 5), and metastatic deposits (N = 26) from 29 patients with invasive SCCP were analyzed, as well as primary (N = 3) and recurrent (N = 2) specimens from 2 patients with penile carcinomain situ(CIS) (Bowen's disease). Nine of the 29 (31%) patients had invasive SCCP containing HPV 16 or 18 DNA, with HPV 16 found in 8 (28%) and HPV 18 in I (3%); no patient had both. In 7 patients in which only tissue from metastatic sites was available, 2 had HPV 16 detected in 2 separate metastatic sites each. Specimens from both primary and metastatic sites were available in an additional 6 patients, and HPV 16 was defected in specimens from 3 of these 6 patients. HPV was detected in comparable copy number at both sites in each patient, indicating that HPV DNA may be a stable component within cancer cells during disease progression. Of patients with CIS only, I of 2 was positive for HPV 16, and upon multifocal recurrence, showed persistence of the virus at 2 separate sites. Southern blotting was performed to confirm the presence of type‐specific HPV DNA and showed complete concordance with D‐PCR, but discordant hybridization intensities for HPV 18 were noted between the control and positive patient specimens; sequence analysis of the patient specimen revealed 4 point mutations in the HPV‐18 target segment. Comparison of the HPV‐positive (both HPV 16 and HPV 18) and HPV‐negative groups revealed no statistical differences between groups in patient age or ethnic origin, tumor histologic grade, or incidence of nodal involvement. Kaplan‐Meier analysis of both overall and cause‐specific survival likewise was not different between groups. These data, particularly the presence of HPV in metastatic deposits, provide strong evidence for an etiologic role of HPV type 16 (and possibly 18) in a substantial sub‐set of patients from the southeastern United States who developed SCCP.
Micronucleus formation in peripheral‐blood lymphocytes from smokers and the influence of alcohol‐ and tea‐drinking habits
Authors: Xue Kai‐Xian , Wang Su , Ma Guo‐Jian , Zhou Ping , Wu Pan‐Quan , Zhang Rui‐Feng , Xu Zhen , Chen Wen‐Sheng , Wang You‐Qin
Published: February 2007

In recent years, studies on the genotoxic effects of smoking and its modifying factors have been widely followed with interest. In this report, frequencies of micronuclei (MNF) in peripheral‐blood lymphocytes in 220 healthy smokers have been detected by the micronucleus test by finger‐skin puncture, which needs only 1 to 2 drops of peripheral blood. On the basis of analysis of matched‐pair data, the modifying effects of alcohol and tea are discussed. Our results show that (1) smoking significantly increases MNF in lymphocytes as compared with healthy non‐smokers (p < 0.01); (2) alcohol significantly increases MNF in smokers (p < 0.01); (3) tea decreases MNF induced by smoking (p < 0.01). Therefore, the anti‐carcinogenic role of tea merits further study.
Immunohistochemical evaluation of parathyroid hormone‐related protein (PTHrP) in the uterine cervix
Authors: Kitazawa Sohei , Kitazawa Riko , Fukase Masaaki , Fujimori Takahiro , Maeda Sakan
Published: February 2007

We investigated the immunohistochemical localization of parathyroid hormone‐related protein (PTHrP), a major factor responsible for the humoral hypercalcemia of malignancy, in uterine cervical lesions. Formalin‐fixed paraffin‐embedded specimens from 16 cases of normal and reactive conditions, 45 cases of cervical intra‐epithelial neoplasm (CIN) and 63 cases of invasive cancer were studied immunohistochemically by the avidine‐biotin‐peroxidase method, using an anti‐PTHrP monoclonal antibody (MAb), 4B3. In normal and reactive conditions, PTHrP was positive in parabasal cells, squamous metaplasia, and hyperplastic reserve cells. In neoplastic conditions, 96% (43/45) of invasive squamous‐cell carcinomas were positive for PTHrP, regardless of the patients' serum calcium levels. Two cases with hypercalcemia were strongly positive for PTHrP and showed prominent stromal interaction of the scirrhous type. In CIN, including koilocytic atypia, 76% (32/42) of cases were positive for PTHrP. In contrast, 91% (10/11) of adenocarcinomas were negative for PTHrP. In conclusion, we found, first, that in non‐neoplastic conditions, the presence of PTHrP was correlated with the transformation of progenitor cells into squamous epithelia and with the maturation of keratinocytes and, second, that in squamous‐cell carcinoma, the degree of keratinization and stromal interaction was higher in direct proportion to the apparent incidence of detectable PTHrP.
Nitrate and N‐nitrosoproline excretion in two italian regions with contrasting rates of gastric cancer: The role of nitrate and other factors in endogenous nitrosation
Authors: Knight T. , Pirastu R. , Palli D. , Cocco P. , Leach S. , Packer P. , Iannarilli R. , Manca P. , Møller H. , Forman D.
Published: February 2007

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25–40 years, residing in areas of Italy with long‐standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N‐nitrosoproline test (NPRO‐test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high‐risk subjects (p = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L‐proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary‐questionnaire‐assessed intake of anti‐oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L‐proline.
Patterns of growth and differentiation in the colon carcinoma cell line lim 1863
Authors: Hayward Ian P. , Whitehead Robert H.
Published: February 2007

The LIM 1863 colon carcinoma cell line grows in the form of morphologically and functionally organized organoids. Cells are arranged around a central lumen with a brush border and nuclei are polarized to the periphery. The organoids contain 3 morphological cell types (columnar, goblet and caveolated cells). By agar cloning it has been possible to isolate 29 subclones of the cell line, all of which display the same phenotype and percentage of morphological cell types as the parent line. Cell‐sorting experiments showed that precursor cells of LIM 1863 cultures could express either mucin (large‐intestinal‐mucus antigen) or a brush‐border enzyme (sucrase‐isomaltase). Proliferating cells were predominantly found near the outer periphery of organoids with cell maturation towards the internal lumen. Dead cells were continuously shed from the organoids but terminal non‐cycling cells were not observed within the organoids. The organoid structure was calcium‐dependent and promoted cell survival. Suspension cultures of disaggregated cells could be grown in medium containing less than 100 μM calcium. No decrease in differentiation antigens was observed in the low‐calcium cultures, although polarization of the cells was lost. The organoid cultures formed by this cell line represent a unique in vitro model for colonic crypt growth and organization.
Reconstituted basement membrane (matrigel) promotes the survival and influences the growth of murine tumors
Authors: Vukičević Slobodan , Somogyi Lehel , Martinović Igor , Žic Rado , Kleinman Hynda K. , Marušić Matko
Published: February 2007

The effects of reconstituted basement membrane (Matrigel) on in vivo survival and growth of several murine tumors were studied. Survival of tumor cells was enhanced in all experiments which resulted in increased incidence and/or in increased tumor mass. While basement membrane enhanced the in vivo growth of B16F6 melanoma cells, survival of these mice was prolonged. Basement membrane increased the incidence but reduced the growth of Ehrlich ascites tumor. Walker‐256 hypercalcemic breast carcinosarcoma growth was enhanced and glandular‐like structures were observed when grown on Matrigel. The results indicate that the enhanced survival of tumor cells in the presence of basement membrane is not unequivocally linked with increased malignancy.
An idiotypic replica of carcinoembryonic antigen inducing cellular and humoral responses directed against human colorectal tumours
Authors: Durrant L. G. , Denton G. W. L. , Jacobs E. , Mee M. , Moss R. , Austin E. B. , Baldwin R. W. , Hardcastle J. D. , Robins R. A.
Published: February 2007

A monoclonal anti‐idiotypic antibody (anti‐Id MAb) 708 (IgG2b), which inhibited the binding of NCRC23 (IgG1) MAb to CEA and prevented radiolabelled CEA from binding to MAb NCRC23, was produced. No recognition of 3 other anti‐CEA antibodies, 3 other IgG1 or 2 IgM MAbs was observed with this anti‐idiotypic antibody. When an immunoblotting technique was used, 708 anti‐Id MAb failed to bind to isolated heavy or light chains of MAb NCRC23, whereas binding was observed with intact antibody. Mouse, rat and human lymphocytes (in vitro) were immunized with 708 anti‐Id MAb and the resultant Ab3 antibodies all inhibited binding of labelled 708 anti‐Id MAb to MAb NCRC23 and also reacted with CEA, showing that 708 anti‐Id MAb induced anti‐CEA antibody responses. Similarly, mice immunized with 708 anti‐Id MAb could be restimulated in vitro with either CEA or tumour cells expressing CEA which induced specific T‐cell proliferative responses. Human tumour‐infiltrating lymphocytes isolated from colorectal tumours or peripheral blood T cells from cancer patients were stimulated in vitro with 708 anti‐Id MAb or an irrelevant IgG2b antibody. Six days later both sets of lymphocytes were restimulated with CEA, and lymphocytes primed to 708 anti‐Id MAb proliferated in response to CEA. These results suggest that 708 anti‐Id MAb can act as an idiotypic replica of CEA and stimulate cellular and humoral anti‐CEA immune responses. It is therefore of great interest as an idiotypic vaccine against colorectal cancer.
Cellular heterogeneity of DNA/total‐protein content in human lung tumors, as determined by flow cytometry
Authors: Teodori L. , Trinca M. L. , Salvati F. , Berettoni L. , Storniello G. , Göhde W.
Published: February 2007

With the aim of distinguishing neoplastic cell sub‐populations of different prognostic and diagnostic significance, dual‐parameter measurements (DNA/protein) have been simultaneously determined in a (256, 256) channel matrix in lung samples derived from 110 patients affected by neoplastic and non‐neoplastic lung diseases. Biparametric analysis demonstrated that cells with abnormally high red fluorescence (i.e., protein content), which is indicative of unbalanced growth, were often observed in malignant tumors as compared with normal lung samples. Furthermore, the dual‐parameter analysis allowed recognition of additional aneuploid tumor‐cell lines, indicating that the frequency of cytometrically determined diploid tumor is lower than that previously described by DNA monoparametric analysis. The recognition of aneuploid sub‐populations by dual‐parameter analysis in clinically and histologically negative one‐parameter flow‐cytometric “diploid” samples assumes important diagnostic value. The results have also shown the presence of multiple protein sub‐populations in clones with the same ploidy value, indicating a higher level of cellular heterogeneity than demonstrated by DNA monoparametric measurements.
Human breast cancer: Concerted role of diet, prolactin and adrenal C19‐Δ5‐steroids in tumorigenesis
Authors: Adams John B.
Published: February 2007

The low incidence of breast cancer in japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast‐cancer risk in post‐menopausal, but not pre‐menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5‐androstene‐3p, 17p‐diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.
p53 expression and prognosis in gastric carcinoma
Authors: Martin Hilary M. , Filipe M. Isabel , Morris Richard W. , Lane David P. , Silvestre Frederico
Published: February 2007

Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene.

In this investigation a 3‐layered immunoperoxidase technique was applied to routinely fixed and paraffin‐embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti‐p53 antibody (CM‐1).

We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel‐Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5‐year survival of patients with p53‐expressing tumours was 24%, compared with 56% for those non‐p53‐expressing tumours (the median survival times were 13 and 102 months, respectively).
Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in epstein‐barr‐virus‐positive nasopharyngeal carcinoma cells
Authors: Busson Pierre , Zhang Qin , Guillon Jean‐Michel , Gregory Christopher D. , Young Lawrence S. , Clausse Bernard , Lipinski Marc , Rickinson Alan B. , Tursz Thomas
Published: February 2007

Undifferentiated nasopharyngeal carcinoma (NPC) is a remarkable entity among human tumors because of its constant association with the Epstein‐Barr virus (EBV). Malignant epithelial cells harbor the EBV genome and often express at least 2 species of latent EBV protein (EBNA1 and LMP1). Despite the massive presence of tumor‐infiltrating lymphocytes, NPC cells obviously escape immune surveillance directed to EBV antigens. Previous investigations carried out on EBV‐positive Burkitt lymphoma (BL) cells have shown that this fact may be partially accounted for by a lack of expression of ICAM1 (CD54) and LFA3 (CD58). ICAM1 and LFA3 have therefore been investigated in fresh NPC biopsies and transplanted NPCs. With only I exception out of 9 cases, NPC cells appear to express high levels of ICAM I and low levels of LFA3. This is a complete inversion of the pattern observed in normal epithelial cells in vivo. Additional investigations will be required to determine to what extent these characteristics affect T‐cell interactions with NPC cells, specially in the process of EBV‐antigen recognition.
Cancer mortality after iodine‐131 therapy for hyperthyroidism
Authors: Hall Per , Berg Gertrud , Bjelkengren Göran , Boice John D. , Ericsson Ulla‐Britt , Hallquist Arne , Lidberg Monika , Lundell GÖRan , Tennvall Jan , Wiklund Kerstin , Holm Lars‐Erik
Published: February 2007

Cancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131l between 1950 and 1975. The patients were matched with the Swedish Cause‐of‐Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.
Oral contraceptives and risk of benign proliferative epithelial disorders of the breast
Authors: Rohan Thomas E. , L'Abbé Kristan A. , Cook Martin G.
Published: February 2007

In a case‐control study conducted in Adelaide, South Australia, we investigated the hypothesis that use of oral contraceptives is associated with increased risk of benign proliferative epithelial disorders (BPED) of the breast, conditions strongly associated with increased risk of breast cancer and thought to have pre‐malignant potential. The study was restricted to women with no prior history of breast biopsy, and involved 383 cases of biopsy‐confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases by age and socio‐economic grading of area of residence. When cases were compared with community controls, the adjusted odds ratio (OR) for the association between ever‐use of oral contraceptives and risk of BPED was 1.1 (95% CI 0.7 to 1.7), while when cases were compared with biopsy controls, the adjusted OR was 0.9 (95% CI 0.5 to 1.5). There was little variation in risk of BPED with total duration of use of oral contraceptives, and with duration of use before first pregnancy, while current users had a statistically significant 60% reduction in risk, irrespective of the control group used for comparative purposes. Also, there was little variation in risk with years since first and last use of oral contraceptives, and there was no trend in the association between ever‐use of oral contraceptives and risk of BPED by degree of cytological atypia.
in vitro and in vivo detection of somatostatin receptors in human malignant lymphomas
Authors: Reubi J. C. , Waser B. , Van Hagen M. , Lamberts S. W. J. , Krenning E. P. , Gebbers J.‐O. , Laissue A. J.
Published: February 2007

A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS‐Rs). We evaluated the SS‐R status of malignant lymphomas that had been surgically removed from 31 patients, by use of in vitro SS‐R autoradiography with the SS analog 1251‐[Tyr3]‐octreotide as radioligand. Of 11 low‐grade‐malignancy B‐cell non‐Hodgkin's lymphomas, 10 were SS‐R‐positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate‐grade lymphomas were SS‐R‐positive. Of the B‐cell lymphomas of high‐grade malignancy, 7 out of 10 were SS‐R‐positive, often with a high density of receptors. One T‐cell lymphoma and one Hodgkin's lymphoma were also positive. SS‐Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma‐camera scintigraphy after i.v. injection of the SS analog IIIIn‐[DTPA‐D‐Phe]‐octreotide. Hot spots, identified in all 4 patients, corresponded to SS‐R‐positive malignant‐lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS‐Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.
Oestrogen sulphatase activity in hormone‐dependent and hormone‐independent breast‐cancer cells: Modulation by steroidal and non‐steroidal therapeutic agents
Authors: Purohit A. , Reed M. J.
Published: February 2007

Oestrogen sulphatase may play an important role in providing intracellular oestrogens from E1S for the growth and maintenance of breast tumours. In this study, we characterized oestrogen sulphatase in the hormone‐dependent (ER/PR+) MCF‐7 and in the hormone‐independent (ER/PR ) MDA‐MB‐231 breast‐cancer cells and, furthermore, examined its modulation by MPA, 4‐OH‐A4, tamoxifen, danazol, ethinyloestradiol and DMAS in both these cell types. Our detailed study of oestrogen sulphatase activity as a function of incubation time, E1S concentration and numbers of MCF‐7 and MDA‐MB‐231 cells showed that more E1S was hydrolysed by MDA‐MB‐231 cells than by MCF‐7 cells at all time points and all substrate concentrations. Additionally, although the km values of E1S for oestrogen sulphatase in both MCF‐7 and MDA‐MB‐231 cells were similar, the Vmax values, and therefore the activity, differed greatly. The effect of various steroidal and non‐steroidal compounds also suggested differences in these 2 cell lines with respect to oestrogen sulphatase inhibition or stimulation. MPA significantly increased the hydrolysis of [3H]E1S in both cell lines, possibly through its effect on membrane fluidity. Tamoxifen increased E1S hydrolysis in MDA‐MB‐231 cells but not in MCF‐7 cells, whereas 4‐OH‐A4 inhibited E1S in MCF‐7 cells but not in MDA‐MB‐231 cells. Danazol (an isoxazol derivative of 17α‐ethinyltestosterone), 17α‐ethinyloestradiol and DMAS all significantly inhibited oestrogen sulphatase activity in both cell lines. Furthermore, danazol had a growth‐inhibitory effect on both MCF‐7 and MDA‐MB‐231 cells, although MCF‐7 cells appeared to be more sensitive to growth inhibition by danazol.
The mechanism of hepatic uptake of a radiolabelled monoclonal antibody
Authors: Boyle Catherine C. , Paine Alan J. , Mather Stephen J.
Published: February 2007

Clinical and experimental scintigraphic studies have found that radiolabelled antibodies are not only taken up by tumour (s) but also by normal liver. The accumulation of radio nuclides in this organ poses a major problem to the use of radiolabelled antibodies as diagnostic and therapeutic tools. In an attempt to understand the mechanism of hepatic uptake and clearance of radiolabelled antibodies, the intrahepatic biodistribution of an 111In‐labelled MAb (HMFGI), was determined following i.v. administration to normal male rats. Two hours after administration the liver contained 15% of the injected dose, with most of the remaining radioactivity in the blood. The hepatic burden of the 111 In MAb remained constant over the next 72 hr in the face of decreasing blood levels of radioactivity as well as its urinary and faecal excretion. At 2 and 72 hr after injection, 50% and 10% respectively of the hepatic radiolabel was due to blood borne antibody. Following a collagenase‐cell isolation procedure, only 23% of the amount remaining in the liver at 2 hr was found to be cell‐associated; 66% was lost during the cell isolation and purification procedure. Cellular uptake increased with time so that, by 72 hr after administration, 58% was cell‐associated and 29% freely removable. At all timepoints, the parenchymal cells contained more activity than non‐parenchy‐mal cells. No evidence of antibody‐receptor interactions could be obtained either in vivo or in cultures of hepatic parenchymal and non‐parenchyma) cells. Our data suggest that the bulk of the hepatic burden of 111In MAb results from extra vascular pooling of the antibody.
Post‐transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells
Authors: Henderson B. R. , McDonald D. A. , Kefford R. F.
Published: February 2007

The regulation of urokinase plasminogen activator (uPA) expression was investigated in 2 highly metastatic rat mammary adenocarcinoma cell lines, BCI and MAT 13762. BCI cells were observed to synthesize, on average, 10 times less uPA enzyme and mRNA than MAT 13762 cells; however this difference was not accounted for by differences in uPA gene copy number/ structure or in the rate of uPA gene transcription in the cell lines studied. Moreover, Northern blot analysis of invasive sub‐populations derived in vitro from the BCI cell line revealed levels of uPA expression similar to those of the parent, but a 3‐fold elevation in expression of the metalloprotease gene, transin. Further investigation showed that treatment of BCI cells with either of the protein synthesis inhibitors, cycloheximide or anisomycin, increased the level of both nuclear and cytoplasmic uPA RNA 6‐ to 18‐fold in 4 hr, whilst inducing a maximum 2.6‐fold increase in the rate of uPA gene transcription. This increase in uPA gene expression may therefore reflect, in part, an increase in the stability and/or processing of nuclear uPA transcripts. These results suggest that the degree of uPA gene expression does not correlate directly with BCI tumor‐cell invasion in vitro, and that the uPA gene is down‐regulated, at least in part, post‐transcriptionafly in the nucleus of BCI mammary tumbr cells.
Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate)
Authors: Van Der Meeren A. , Fleury J. , Nebut M. , Monchaux G. , Janson X. , Jaurand M. C.
Published: February 2007

Pathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface‐modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: I untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were > 8 μm in length and < 0.25 μm in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile.
Use of multi‐cell spheroids of ovarian carcinoma as an intraperitoneal radio‐immunotherapy model: Uptake, retention kinetics and dosimetric evaluation
Authors: Bardiès Manuel , Thedrez Philippe , Gestin Jean‐Francois , Marcille Berthe‐Marie , Guerreau Dominique , Faivre‐Chauvet Alain , Mahe Marc , Sai‐Maurel Catherine , Chatal Jean‐François
Published: February 2007

The purpose of this study, using multi‐cell spheroids as an in vitro model of micrometastases of ovarian carcinoma for i.p. radio‐immunotherapy, was to measure the uptake and retention kinetics of 'In‐labeled F(ab')2 fragments of OCI25 monoclonal antibody (MAb) in spheroids of the NIH:OVCAR‐3 cell line and to estimate absorbed doses with beta‐emitting radionuclides (kinetics was assumed to be similar to that of indium‐111). With 0.2‐mm‐diameter spheroids at different MAb concentrations the highest binding value was determined. Retention kinetics showed a biological half‐life of 50 hr. These data were used to calculate absorbed doses by integration of Berger's latest‐point kernels. Mean absorbed doses when spatial distribution was considered to be uniform at the surface (no penetration) or throughout the spheroid (total penetration) were, respectively, 247 and 417 Gy with 153Sm, and 90 and 135 Gy with 90Y. Thus, the use of a similar MAb concentration and specific activity in patients should lead to high absorbed doses in i.p. radio‐immunotherapy of micrometastases.
Diet and gastric cancer. A case‐control study in Belgium
Authors: Tuyns Albert J. , Kaaks Rudolf , Haelterman Margareta , Riboli Elio
Published: February 2007

A case‐control study was carried out in 2 Belgian provinces with contrasting gastric‐cancer mortality. The results were analyzed for the total study group and also separately in each of the 4 sub‐groups: men and women in each province. Only risks which appeared consistently in at least 3 of these 4 sub‐groups were retained in the discussion. Consumption of most vegetables, either cooked or raw, and of fresh fruit was found to be protective. There was an increased risk associated with meal and flour products, including white bread. Added sugar also increased the risk of gastric cancer. Consumption of lean meat was associated with a decreased risk. There was no clear effect for most sources of fat, but for oils with a high P/S ratio there was a decreased risk. Together with our earlier finding on salt, these results are to a large extent similar to those of other recent studies on gastric cancer.
Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I‐labelled anti‐tenascin monoclonal antibody BC‐2
Authors: Riva P. , Arista A. , Sturiale C. , Moscatelli G. , Tison V. , Mariani M. , Seccamani E. , Lazzari S. , Fagioli L. , Franceschi G. , Sarti G. , Riva N. , Natali P. G. , Zardi L. , Scassellati G. A.
Published: February 2007

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC‐2, raised against tenascin and labelled with 131I. Tenascin, the BC‐2‐recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti‐tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC‐2 uptake was 4.9% per gram and its effective half‐life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (>50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after 11 months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.
Body measurements, estrogen availability and the risk of human breast cancer: A case‐control study
Authors: Bruning P. F. , Bonfrèr J. M. G. , Hart A. A. M. , van Noord P. A. H. , van der Hoeven H. , Collette H. J. A. , Battermann J. J. , de Jong‐Bakker M. , Nooijen W. J. , de Waard F.
Published: February 2007

Recent studies on lifestyle‐related mechanisms involved in cardiovascular risk offer important clues for a better understanding of breast‐cancer epidemiology. Central body‐fat distribution promoted by an affluent dietary intake and a sedentary lifestyle over many years is related to elevated serum triglycerides and free fatty acids, with lower levels of sex‐hormone‐binding globulin (SHBG). The resulting greater availability of estradiol not bound to SHBG could help to explain the high breast‐cancer incidence in Western industrialized countries.

We conducted a case‐control study comparing 225 women aged 38 to 75 years with operable (stage I or II) breast cancer and 441 women of the same age having no breast cancer who participated in a population‐based breast‐cancer screening program. Body fatness, as measured by body mass index (BMI), fat distribution as measured by waist‐to‐hip girth ratio (WHR), body height, serum lipids, SHBG and the available fraction of estradiol were analyzed in a conditional logistic regression, together with family history for breast cancer, reproductive history and smoking.

Post‐menopausal cases showed no difference in body fatness (BMI), but a significant preponderance of central adiposity (WHR). In contrast, pre‐menopausal cases were significantly leaner, but had a similar body‐fat distribution as compared with controls. In all women, WHR, and less strongly BMI, was positively correlated with serum levels of triglycerides and available estradiol fractions. An independent, positive linear correlation between body height and relative risk (RR) was observed. Moreover, a significant correlation between SHBG and menarcheal age was seen in cases, but not in controls.

These data support our hypothesis that lifestyle relates to breast‐cancer risk by metabolic‐endocrine mechanisms which modulate the availability of individual sex‐steroid concentrations in plasma. The findings of height as a risk factor and adult SHBG levels being correlated with menarcheal age suggest that lifestyle factors promoting breast‐cancer development already act around puberty. The leanness of pre‐menopausal cases awaits further explanation.
Pre‐cancerous lesions of the oesophagus in Argentina: Prevalence and association with tobacco and alcohol
Authors: Castelletto R. , Muñoz N. , Landoni N. , Jmelnitzky A. , Crespi M. , Belloni P. , Chopita N. , Teuchmann S.
Published: February 2007

The prevalence of pre‐cancerous lesions of the oesophagus and their association with alcohol and tobacco were examined in an endoscopic survey carried out in La Plata, Argentina. The study included 406 subjects over 15 years of age attending several gastroenterology clinics because of various gastrointestinal symptoms. Among males, the prevalence rates of chronic oesophagitis, epithelial atrophy and dysplasia were 42%, 3.8% and 2.4% respectively, and in females these prevalences were 36%, 2.5% and 0.0%. The presence of these pre‐cancerous lesions was significantly associated with alcohol drinking and tobacco smoking.
Maternal and perinatal risk factors for Wilms' tumor: A nationwide nested case‐control study in Sweden
Authors: Lindblad Per , Zack Matthew , Adami Hans‐Olov , Ericson Anders
Published: February 2007

This report describes maternal and perinatal risk factors for Wilms' tumor analyzed in a case‐control study nested in a nationwide cohort in Sweden. The Swedish National Cancer Registry ascertained 110 cases from among successive birth cohorts from 1973 through 1984, identified by the Swedish Medical Birth Registry, the latter based on medical records. From the Birth Registry, we matched 5 controls without cancer to each case by sex and date of birth. Wilms'‐tumor children were more likely to have mothers who had been exposed to penthrane (methoxyflurane) anesthesia during delivery than mothers of controls (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.1 to 5.1); this excess risk was higher in females than males and increased with age at diagnosis. Wilms'‐tumor cases were also more likely to have had physiologic jaundice (OR = 2.3; 95% CI 1.1 to 5.0). Higher parity of the mother decreased the risk of Wilms' tumor among females (OR = 0.7; 95% C1 0.5 to 1.0). We were unable to confirm the reported increased risks of Wilms' tumor for those with high birth weights or with a maternal history of hypertension or fluid retention during pregnancy, nor did we find any association with mother's age at delivery, previous stillbirth, previous live birth, gestational length or height of the child.
Chromosomal deletions and K‐ras gene mutations in human endometrial carcinomas
Authors: Imamura Toshiro , Arima Takahiro , Kato Hidenori , Miyamoto Shingo , Sasazuki Takehiko , Wake Norio
Published: February 2007

Forty‐two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int‐2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico‐pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K‐ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juveniletype adenocarcinomas and 2 clear‐cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub‐sets during carcinogenesis are probably heterogeneous.
CA125‐response assessment in epithelial ovarian cancer
Authors: Cruickshank D. J. , Terry P. B. , Fullerton W. T.
Published: February 2007

To assess the clinical potential of serial serum CA125 measurements in the follow‐up of patients with epithelial ovarian cancer, 74 consecutive unselected patients with histologically confirmed ovarian carcinoma were studied prospectively. There was an 83% concordance between clinical assessment and CA 125 assessment of response. The positive predictive values of a rising CA125 for disease progression and a falling CA125 for disease regression were 0.93 and 0.94, respectively. The absolute CA125 values during observations of complete response (mean 96 U/ml; 95% confidence interval; 33 to 128 U/ml), partial response (mean 134 U/ml; 95% confidence interval; 98 to 159 U/ml) and stable or progressive disease (mean 391 U/ml; 95% confidence interval; 282 to 545 U/ml) were significantly different. A randomized study is required to determine whether CA125 monitoring has any benefit in terms of outcome, and particularly survival, in epithelial ovarian cancer.
Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients
Authors: Iwahashi Makoto , Tanimura Hiroshi , Yamaue Hiroki , Tsunoda Takuya , Tani Masaji , Tamai Mikiko , Noguchi Kohei , Hotta Tsukasa
Published: February 2007

The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR‐killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR‐killer cells against various tumor‐cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumorkilling activity of AMLR‐killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD 16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non‐specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non‐specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.
Expression of myc‐family genes in established human multiple myeloma cell lines: L‐myc but not c‐myc gene expression in the U‐266 myeloma cell line
Authors: Jernberg‐Wiklund H. , Pettersson M. , Larsson L‐G. , Anton R. , Nilsson K.
Published: February 2007

Deregulated c‐myc expression, as a consequence of translocation of the c‐myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B‐cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma. This study investigated the expression of c‐myc and 2 other members of the myc gene family, L‐ and N‐myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma—multiple myeloma (MM). Nine well‐characterized MM cell lines were examined by using Northern‐ and Southern‐blot analysis and immunoprecipitation. The c‐myc gene was found to be highly expressed in most MM cell lines. The level of expression was comparable to that observed in the COLO 320 and HL‐60 cell lines, carrying amplified c‐myc genes, and to that of B‐cell lines with a higher proliferative activity than the MM cell lines. In the U‐266 MM cell line, L‐myc, but no c‐myc mRNA or protein, was found. The L‐myc gene was expressed in both early‐ and late‐passage U‐266 cells, suggesting that the L‐myc expression was not the result of the in vitro cultivation. N‐myc was not expressed in any of the MM cell lines. No rearrangements of c‐myc or L‐myc genes were found. We thus conclude that (a) in contrast to the corresponding mouse and rat B‐cell tumors, c‐myc is not frequently rearranged in MM; (b) c‐myc is highly expressed in most MM lines; and (c) L‐myc but not c‐myc is expressed in the U‐266 MM cell line.
Reactivity to TGF‐β is one step towards transformation in a murine fibroblast cell line
Authors: Götschl Michaela , Höfler Petra , Bauer Georg
Published: February 2007

High doses of TGF‐β induce reactivity to TGF‐β in a distinct number of C3H10T1/2 fibroblasts suspended in soft agar. Reactive cells can be isolated and stably maintain this property. In the absence of exogenously added TGF‐β, these cells do not form colonies, but show distinct changes in their morphology and cytoskeleton. In contrast to normal C3H10T1/2 cells, they are able to form colonies when low doses of TGF‐β are added. TGF‐β‐reactive cells are more easily transformed by UV light than normal C3H10T1/2 cells, and so maintain their transformed phenotype in the absence of added TGF‐β. Reactivity for TGF‐β, therefore, represents one step towards transformation.
An in vitro fibroblast model system to study myc‐driven tumour progression
Authors: Chisholm Orin , Symonds Geoff
Published: February 2007

We have utilized fibroblast cell lines to investigate myc‐mediated cell transformation and tumour progression. Deregulated myc alleles were introduced into the rat fibroblast cell line, Rat‐1, and a partially‐transformed derivative of this cell line termed Rat‐1(PT). A human c‐myc gene coupled to the Moloney murine leukemia virus long terminal repeat was introduced into both cell lines by transfection. The avian MC29 v‐myc gene was introduced into the Rat‐1 cell line by retroviral infection using a Moloney murine leukemia recombinant retrovirus. For both cell lines, the introduction of exogenous myc genes resulted in an increased degree of transformation. For the non‐tumorigenic Rat‐1 cell line, this also resulted in the acquisition of tumorigenicity, while for the Rat‐1(PT) cell line the degree of tumorigenicity was increased. Various clones were isolated and, for both human c‐myc and avian v‐myc, the level of myc expression correlated with the degree of transformation and the tumorigenic potential of the cell lines. In addition, both these parameters could be increased by passaging through syngeneic recipients. Our data show that tumour progression may be driven by the deregulated expression of myc genes; that transformation and tumorigenicity correlate with the level of exogenous myc expression; that additional events involving both in vitro and in vivo selection are involved in this process; and that myc expression may increase the cells' metastatic capacity.
The geography of non‐ocular malignant melanoma in India: its association with latitude, ozone levels and UV light exposure
Authors: Krishnamurthy Sarala
Published: February 2007

Ultraviolet light from sunlight is implicated in the aetiology of non‐ocular malignant melanoma, mostly from Western studies. This study reports the relation of such melanomas from 7 cancer registries in different parts of India with latitude, altitude, ozone levels and ultraviolet (UV) light exposure. A log linear model was fitted using GLIM, assuming Poisson errors in incidence; linear and non‐linear regression techniques were also used. Results show slight negative associations of melanoma with latitude, X2 = ‐3.37, p = 0.07, and statistically nonsignificant ones with atmospheric ozone levels (r = ‐0.36, n.s.), and a positive association with UV (r = 0.30, n.s.). Melanoma incidence from 4 places relates in a parabolic curve with latitude (y = I‐0.09 X2 + 0.003 X2 in males and y = 1.73–0.17 X2 + 0.005 X2 in females). Patients originally from west coastal ethnic/linguistic communities predominate in Bombay. Geographic patterns of melanoma in Indians are similar with those in white Caucasians. Ultraviolet light exposure may also be involved in its aetiology in non‐white Caucasians, such as Indians.