bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer of the nasal cavity and paranasal sinuses, and formaldehyde exposure
Authors: Hayes Richard B. , Raatgever Jan W. , de Bruyn Arry , Gerin Michel
Published: February 2007

This case‐control study of nasal and paranasal sinus tumors, in males diagnosed between 1978 and 1981 in the Netherlands, was designed to identify environmental risk factors. Special attention was given to assessing any association between nasal cancer and an occupational history of possible formaldehyde exposure while taking into account histologic type of tumor, history of tobacco use, and occupational exposure to wood dust. Of the 116 cases and 259 controls identified, interviews were completed for 91 (78%) of the cases and 195 (75%) of the controls.

Adenocarcinoma was strongly associated with a history of high wood dust exposure (RR = 27.0). Two independent assessments of the association between possible formaldehyde exposure and the risk for nasal cancer were carried out (Assessments A and B). By Assessment A the relative risk for nasal cancer associated with possible formaldehyde exposure was 2.5 and by Assessment B it was 1.9. The risk appeared to be most strongly associated with squamous‐cell carcinoma and could not be attributed to differences between cases and controls in age, smoking habits, or wood dust exposure. By its retrospective nature, the classification of formaldehyde exposure in this study is not based on known exposures to formaldehyde but on assessment of employment in jobs where formaldehyde exposure is thought possible. Given the limitations of the study, the authors do not consider that it provides conclusive evidence of a carcinogenic effect for formaldehyde, but that it indicates a need for further research–particularly into formaldehyde and squamous carcinoma of the nose.
Lysis of autologous tumor cells by high‐density lymphocytes is potentiated by the streptococcal preparation OK432 (picibanil)
Authors: Vánky Farkas , Uchida Atsushi , Klein Eva , Willems Jan
Published: February 2007

In experiments performed with tumor cells isolated from surgical specimens and lymphocytes collected at the time of surgery, tumor cells are often lysed by blood lymphocytes. Some of the effectors are present in the high‐density T‐cell subset. This population has little or no anti‐K562 activity. For the auto‐tumor lysis of T‐cells with high density, CD8‐positive cells are mainly responsible. OK432 pretreatment of the effectors potentiates the existing lytic function or induces it in cases in which the cells have no such function. In general, the potentiating effect reflects inherent patterns of cytotoxicity. In contrast to the lysis of autologous tumor cells, cells with low but not high density were induced to lyse K562.
Comparison of risk factors for cervical cancer in different populations
Authors: Rawls William E. , Lavery Carol , Marrett Loraine D. , Clarke E. Aileen , Adam Ervin , Melnick Joseph L. , Best Jennifer M. , Kraiselburd Edmundo , Benedet Louis J. , Brenes Maria M. , Quiroz Evelia , Reeves William C.
Published: February 2007

The incidence of cervical cancer has been found to vary between populations. Risk factors of cervical cancer include early age at first marriage, multiple marriages and antibodies to herpes simplex virus type 2 (HSV‐2). The interrelatedness of these risk factors was examined by comparing data collected from 428 cancer cases and 947 control women selected from 6 populations having standardized cervical cancer incidence rates varying from 9.3 to 85.1 per 100,000. Logistic regression analysis revealed that multiple marriages, early age at first marriage or pregnancy and HSV‐2 antibodies were all associated with significant risk when all 3 factors were entered into the model. Cervical cancer incidence rates were best predicted by the occurrence of HSV‐2 antibodies among control women. To further assess the relation between cervical cancer rates and HSV‐2 antibody, 2,306 additional sera representing an 0.8% random sample of females over 9 years of age residing in the Republic of Panama were assayed for antibodies to the virus, and the occurrence of antibodies was correlated with invasive crvical cancer rates specific to each Province. Data from both the random sample and the other study populations yielded a linear relation between the occurrence of HSV‐2 antibodies and the incidence of cervical cancer. An exception was found for women living in Herrera Province, Republic of Panama, who had a higher cancer rate than predicted by HSV‐2 antibody occurrence. The data suggested that infection with HSV‐2 is a co‐variable of venereal factors, although a role for the virus in the genesis of a certain proportion of cervical cancers is not excluded.
The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice
Authors: Ramani P. , Hart I. R. , Balkwill F. R.
Published: February 2007

A recombinant human hybrid alpha interferon (rIFN‐α A/D) with antiviral, immunomodulating and cell‐growth‐inhibitory activity on murine cells strongly inhibited the development of experimental pulmonary metastases of the Colo 26 adenocarcinoma in BALB/c mice. Twenty‐one days after i.v. injection of 5 × 104 cells, 8/8 control mice had >200 lung tumour nodules whereas 1/6 mice receiving 500 ng rIFN‐α A/D had one lung tumour nodule and the other 5 mice were tumour‐free. Equally strong inhibition was seen in immunodeficient BALB/c nu/nu (athymic) and beige nu/nu (athymic and NK‐deficient) mice. Scheduling experiments in vivo showed that the most important time of IFN treatment was from the day of tumour cell injection to day 5, although statistically significant reductions in lung tumour nodule number and lung weight were seen even when IFN treatment was started 7 days after cell injection. rIFN‐α A/D was cytostatic to Colo 26 in vitro, causing 50% or more inhibition of cell growth or colony number at IFN levels that could be achieved in the sera of IFN‐treated mice. Although rIFN‐α A/D stimulated NK‐cell activity in BALB/c mice, Colo 26 cells were resistant in vitro to such cells whether from control or IFN treated mice.
Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects
Authors: Heicappell R. , Schirrmacher V. , von Hoegen P. , Ahlert T. , Appelhans B.
Published: February 2007

Effective anti‐metastatic therapy was achieved in a mouse tumor model by combining surgery with postoperative immunotherapy using virus‐modified autologous tumor cells. No therapeutic effect was observed when using for immunotherapy the nonmodified autologous tumor ESb, which is only weakly immunogenic and highly metastatic. The viral modification was achieved by infecting the tumor with an avirulent strain of Newcastle disease virus (NDV), which led to expression of viral antigens and to an increase in the tumor cells' immunogenicity. Parameters which were of decisive influence for success or failure of therapy were the time of operation of the primary tumor and the dose of virus which was admixed to a standard dose of irradiated tumor cells. There was a low dose optimum of NDV at about 100 hemagglutinating units per 25 × 106 tumor cells. The therapeutic effect observed was less pronounced if the virus was given separately from the tumor cells. Postoperative immunotherapy with NDV‐modified tumor cells had the following therapeutic effects: (1) disappearance of micrometastases from visceral organs as ascertained by a sensitive bioassay; (2) life prolongation in virtually all animals when compared to controls (operated only); (3) cures in about 50% of the treated animals. The possible mechanism of this therapeutic effect and its potential for clinical application are discussed.
Chemosensitivity profiles of human cancers assessed by the 6‐day SRC assay on serially xenografted tumors
Authors: Aamdal Steinar , Fodstad Øystein , Kaalhus Olav , Pihl Alexander
Published: February 2007

To assess the potential value of the 6‐day subrenal capsule (SRC) assay in preclinical evaluation of new drugs using serially xenografted human tumors as source of tumor tissue, we studied the response of 31 human tumor lines (8 malignant melanomas, 12 sarcomas, 9 lung carcinomas and 2 colon carcinomas) to relevant standard drugs and to a new imidazotetrazine, Mitozolomide. Mitozolomide was found to be the most active drug tested in 50% of the lung carcinomas and as active as CCNU in melanomas. The activity of the standard anticancer drugs against subrenal grafts closely resembled the patterns seen with the same tumors in the clinic. In further attempts to validate the procedure, sensitivity profiles of some tumors were concurrently determined in the subcutaneous (s.c.) nude mouse model. In 11 out of the 12 tumors, the two assays selected the same drug as being the most active and in most of these tumors the two procedures gave the same ranking for the different drugs. Also, when the relative sensitivities of a series of melanoma xenografts to each of two drugs (DTIC and CCNU) were tested, the two assays gave the same ranking of the xenografts for each drug. The concordance between the two assays and the fact that the s.c. nude mouse assay reflects the chemosensitivity of the parent tumor in patients, suggest that the application of the 6‐day SRC assay to xenografted tumors is a valid and useful procedure permitting rapid preclinical evaluation of new drugs to be carried out at relatively low cost.
Lymphokine‐induced monocyte procoagulant activity is depressed in patients with advanced malignancies
Authors: Geczy Carolyn L. , Ryan Jane , Walsh John , Goldstein David
Published: February 2007

Fibrin deposition in the microenvironment of tumor cells may be critical to tumor growth and metastasis formation. Procoagulant activities of tumor cells themselves, or of infiltrating macrophages, activated by the host's immune system to the tumor, may both contribute to coagulopathies associated with metastases. Lymphokine (LK) supernatant activated procoagulant activity on normal peripheral blood monocytes but failed to induce activity on mononuclear cells from 18/22 patients with locally advanced or disseminated non‐lymphoid tumors. Monocytes from the remaining patients had very low basal levels of MPCA and were less sensitive than normal cells to LK. Monocytes from 4 patients (3 with tumors with a high growth fraction) had extremely elevated levels of basal procoagulant activity, possibly due to maximal activation in vivo. Neither LK nor bacterial lipopolysaccharide (LPS) stimulated procoagulant production of these cells. By contrast, cells from 8/13 patients produced procoagulant in response to LPS. This study indicated that monocyte function of patients with disseminated cancer is suppressed with respect to LK stimulation, but that cells with normal basal levels of MPCA respond to LPS. Preactivation of mononuclear procoagulant in vivo precluded subsequent stimulation by either LPS or LK.
Biochemical characterization of the monoclonal antibody‐defined ovarian carcinoma‐associated antigen SGA
Authors: de Kretser Theonne A. , Thorne Heather J. , Picone Diana , Jose David G.
Published: February 2007

The molecular nature of SGA, the ovarian‐carcinoma‐associated antigen defined by the MAb OM‐1, has been determined. The cell‐surface form of the SGA molecule is a glycoprotein with p1 <4.2, which on PAGE analysis has an apparent MW of approximately 360 kDa. This was the only OM‐1‐reactive species found on the cell surface. The apparent MW was unaffected by reducing conditions. The predominant cytoplasmic form of SGA is a non‐glycosylated 170‐kOa molecule with p1 6.5. Pulse‐chase experiments were complicated by the extremely slow rate of SGA synthesis. However, the data indicate that the SGA molecule is synthesized as a 190‐kDa protein, cleaved to yield a 170‐kDa non‐glycosylated intracellular form which is slowly glycosylated to the 360‐kDa cell‐surface species. Western blotting experiments revealed the presence of the 360‐kDa glycosylated molecule in human ovarian cell culture supernatants.
Effects of tumor promoters on growth and on cellular redistribution of phospholipid/CA2+‐dependent protein kinase in human breast cancer cells
Authors: Regazzi Romano , Fabbro Doriano , Costa Serban D. , Borner Christoph , Eppenberger Urs
Published: February 2007

Active, structurally unrelated tumor promoters (12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), teleocidin and aplysiatoxin) inhibit growth of mammary carcinoma cells (MCF7‐>BT‐20>MDA‐MB‐231> = ZR‐75‐1>HBL‐100). This efficiency in inhibiting cell growth correlates with the tumor‐promoting activity of a series of phorbol ester derivatives. The phospholipid/calcium‐dependent protein kinase (PKC), a target for phorbol ester action, was measured by polyacrylamide gel electrophoresis. The levels of PKC were higher (p<0.001) in estrogen‐receptor‐negative than in estrogen‐receptor‐positive cells. Treatment of cells with active tumor promoters results in time‐ and dose‐dependent translocation of cytosolic PKC to membrane fractions. Less potent phorbol esters induce only partial translocation of PKC (i.e., decrease of cytosolic without increase in membrane‐bound PKC), whereas inactive esters have no effect. No correlation was found between PKC concentration or the amount of PKC translocated to membranes and the sensitivity of the respective cells to TPA. It is concluded that tumor‐promoter‐mediated growth inhibition of breast cancer cell lines is due to mechanism(s) occurring after the translocation of PKC.
Promotion of 3′‐methyl‐4‐dimethylaminoazobenzene‐initiated adult rat liver cells to malignant state by phenobarbital in culture
Authors: Miyazaki Masahiro , Handa Yoshihiko , Suzuki Yasunori , Sato Jiro
Published: February 2007

After treatment with 1.5 mm phenobarbital (PB) for about 2 months, non‐tumorigenic rat liver epithelial‐type cell lines (6F‐7 and 6G‐5), which were initiated by 3′‐methyl‐4‐dimethyl‐aminoazobenzene (3′‐Me‐DAB) in primary culture, showed an increase in plating efficiency, growth in soft agar and production of tumors in syngeneic animals. However, the PB‐untreated control cells exhibited neither growth in soft agar nor production of tumors. Gamma‐glutamyltranspeptidase (GGT)‐positive (6F‐7‐cl‐7) and negative (6F‐7‐cl‐8) colonial clones, which were derived from 6F‐7 cells, were also treated with 1.5 mM PB for about 2 months. The growth of GGT‐positive 6F‐7‐cl‐7 cells was not suppressed but rather stimulated by PB at 1.5 mM, whereas that of GGT‐negative 6F‐7‐cl‐8 cells was severely inhibited. Furthermore, the PB‐treated 6F‐7‐cl‐7 cells produced tumors in syngeneic animals, but the PB‐treated 6F‐7‐cl‐8 cells produced no tumors. The spontaneous cell line 6A‐6, which was derived from the 3′‐Me‐DAB‐untreated primary liver cell culture and was GGT‐negative, did not exhibit tumorigenicity after treatment with 1.5 mM PB for the same period of time as described above. In conclusion, PB treatment efficiently and rapidly promoted the 3′‐Me‐DAB‐initiated cells to a malignant state.
Tumour basement membrane laminin in adenocarcinoma of rectum: An immunohistochemical study of biological and clinical significance
Authors: Forster S. J. , Talbot I. C. , Clayton D. G. , Critchley D. R.
Published: February 2007

Well‐defined basement membrane laminin was seen in 98/158 (62%) rectal adenocarcinomas stained by an immunoperoxidase method. Only 27 (28%) patients with laminin‐positive tumours developed distant metastases, compared with 39 (65%) patients with laminin‐negative carcinomas. The corrected 5‐year survival rates for patients with laminin‐positive and laminin‐negative tumours were 65% and 23%, respectively. Twenty‐five out of 30 (83%) well‐differentiated adenocarcinomas and only 3/15 (17%) poorly differentiated tumours contained basement membrane laminin, with moderately differentiated carcinomas showing intermediate laminin status (70/110, 64%, laminin positive). Forty‐three of 60 (72%) of laminin‐negative tumours had metastasized to regional lymph nodes. These data suggest that laminin may be a marker for differentiation. However, laminin status yields information about tumour behaviour which is not confined to stage and grade, and multivariate analysis shows that it is a better indicator of prognosis than tumour grade as assessed by conventional histology. Although laminin status alone is a less useful predictor of prognosis than Dukes' stage, a patient with a laminin‐positive adenocarcinoma of rectum is 2.7 times as likely to survive 5 years than a patient with a laminin‐negative tumour. Assessment of laminin status, together with Dukes' stage is, therefore, commended as a more precise and objective indicator of prognosis than histological degree of differentiation in colorectal carcinoma.
Serial transmission of human T‐cell leukemia virus type I by blood transfusion in rabbits and its prevention by use of X‐irradiated stored blood
Authors: Kotani S. , Yoshimoto S. , Yamato K. , Fujishita M. , Yamashita M. , Ohtsuki Y. , Taguchi H. , Miyoshi I.
Published: February 2007

Human T‐cell leukemia virus type 1 (HTLV‐1) was serially transmitted for 5 passages from rabbit to rabbit by blood transfusion. The virus could be transmitted with 20 ml of whole blood or washed blood cell suspension (fresh or stored for 1–2 weeks at 4°C) but not with cell‐free plasma from seroconverted rabbits. Seroconversion occurred 2–4 weeks after blood transfusion and serum anti‐HTLV‐1 titers ranged from 1:20 to 1:640 with the immunofluorescence assay. From transfusion recipients of the 1st to 4th passages, virus‐producing cell lines were established by culturing lymphocytes in the presence of T‐cell growth factor (TCGF). Three of the 4 cell lines became TCGF‐independent after 2–12 months of continuous culture. Blood was transfused between rabbits of opposite sexes and the recipient origin of each cell line was determined by chromosome analysis. We also investigated the effect of X‐irradiation (6,000 rad) on blood from seropositive rabbits. Seroconversion likewise occurred in rabbits transfused with blood that had been irradiated immediately before transfusion but not in rabbits transfused with blood that had been irradiated and stored for 1–2 weeks at 4°C. Thus, our rabbit model shows that HTLV‐1 is serially transmissible by blood transfusion and that this can be prevented by irradiation of blood. The same procedure, therefore, may be useful for the prevention of transfusion‐related transmission of HTLV‐1 in humans.
New abnormal isoenzyme of 5′‐nucleotide phosphodiesterase in the serum of human hepatoma
Authors: Lin Ke‐Min , Ye Si‐Yuan , Liu Qi‐Fu
Published: February 2007

5′‐nucleotide phosphodiesterase (5′‐NP) isoenzymes were separated from the serum of human primary liver cancer (PLC) patients by 4–20% tubular polyacrylamide gel gradient electrophoresis. Electrophoresis showed II isoenzymes in which bands I, V and VI (from anode to cathode) were all absent in 125 normal control sera; bands V and VI were detectable in 31(73.8%) of 42 patients with PLC, but absent in 70 cases of other diseases. Bands V and VI may represent specific isoenzyme bands of PLC, comprising a new addition to the markers used in the diagnosis of this disease. By the same method, it was also found that the abnormal serum isoenzyme bands of PLC correspond to those found in the cord blood sera of the newborn and fetus. These abnormal isoenzymes diminish gradually after birth and all disappear when children reach the age of 10.
Human papillomavirus DNA sequences in penile carcinomas in Brazil
Authors: Villa Luisa Lina , Lopes Ademar
Published: February 2007

To detect the presence of human papillomavirus (HPV) DNA in penile cancers, 18 squamous‐cell carcinomas were studied by Southern blot analysis. All specimens were from Brazilian patients ranging in age from 31 to 78 years. Of these, 7 harbored DNA sequence homology. Most positive specimens contained more than 100 copies of viral DNA. No HPV 16 was detected in our samples. Presence of HPV DNA sequences in the samples studied was not correlated with the patients' age or race, nor with extent or progress of disease.
Sporadic somatic fusion between MDAY‐D2 murine tumor cells and DBA/2 host cells: Role in metastasis
Authors: Lagarde Alain E.
Published: February 2007

An ouabain‐ and 6‐thioguanine‐resistant mutant (K3T103) of the metastatic MDAY‐D2 murine tumor cell line was transplanted s.c. into syngeneic DBA/2 mice in order to isolate K3T103 x host cell hybrids emerging in vivo, and examine their metastatic potential. Of 10 tumor‐bearing animals that were analyzed at various time intervals, only 3 developed fusion products in the primary site, present at a frequency ranging between 10−5 and 10−4. These hybrids survived in HAT + ouabain medium, had a lymphoblastoid morphology and a hypo‐tetraploid karyotype, were non‐adherent, and were as rapidly metastatic as K3T103 cells when transplanted s.c. or i.v. into DBA/2 mice. All these characteristics were shared by cloned hybrids generated in vitro following polyethylene glycol (PEG)‐mediated fusion of K3T103 cells with normal DBA/2 normal splenocytes. In marked contrast, the products of K3T103 x DBA/2 normal lung fibroblast fusion displayed a fibroblastic appearance, were adherent, progressively ceased to divide and remained dormant for several weeks in culture. These results indicate: (1) that spontaneous fusion of K3T103 cells with host cells in the course of their expansion and subsequent dissemination is a stochastic and rare event, and (2) that since the expression of their tumorigenic and metastatic potential is retained after fusion with splenocytes, host cells of lymphoreticular origin are most likely involved in that process.
Inhibitors of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced multinucleated cell formation and HTLV‐I p19 antigen expression in HTLV‐I‐infected T‐cell line KH‐2Lo
Authors: Nakao Yoshinobu , Matsuda Shuichi , Matsui Toshimitsu , Koizumi Tamio , Katakami Yuko , Fujita Takuo , Ito Yohei
Published: February 2007

To elucidate the biological mechanisms of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced phenotypic changes in HTLV‐I virus‐infected human T‐cell line KH‐2Lo cells, inhibitors of TPA‐induced ornithine decarboxylase (ODC), protein kinases and calmodulin were examined for their effects on TPA‐induced multinucleated cell formation and HTLV‐I p19 antigen expression. Among the inhibitors of TPA‐induced ODC activity, α‐difluoromethyl ornithine (DFMO), I,25(OH)2D3 and its analogues, and retinoic acid were tested. As inhibitors of protein kinases, I‐(5‐isoquinolinyl‐sulfonyl)‐2‐methylpiperazine (H‐7), N‐[2‐(methylamino)ethyl]‐5‐isoquinoline‐sulfonamide (H‐8) and I,(5‐isoquinolynylsulfonyl)‐2,3‐dimethylpiperazine (H‐5) were used. In addition, a calmodulin inhibitor, N‐(4‐aminobutyl)‐5‐chlor‐2‐naphthalenesulfonamide (W13) and its inactive analogue, N‐(4‐aminobutyl)‐2‐naphthalenesulfonamide (W 12) were also tested. I,25(OH)2D3 and its active analogues inhibited both TPA‐induced HTLV‐I p19 antigen expression and multinucleated cell formation after 4 days of culture with TPA. On the other hand, an inhibitor of ODC, DFMO, the protein kinase inhibitors, the calmodulin inhibitor and retinoic acid suppressed TPA‐induced HTLV‐I p19 expression but did not suppress multinucleated cell formation.
Cancer in Haiti 1979–84: Distribution of various forms of cancer according to geographical area and sex
Authors: Mitacek E. J. , Vallieres D. St. , Polednak A. P.
Published: February 2007

Haiti exemplifies all of the problems of developing countries: poverty, hunger, reduced longevity, and an illiteracy rate of more than 75%. It is, therefore, not surprising that so little attention has been given to late‐onset chronic diseases, particularly cancer. The results of a special survey of cancer cases first diagnosed in 1979–84 are presented, with relative proportions of cancers by site, according to age, sex and geographical area of origin (coastal vs. mountain). The major cancers recorded were: stomach and intestine, primary hepatic (especially in males), cervix, penis, and Kaposi's sarcoma (KS). There were 18 cases of KS, all of which occurred among AIDS patients. Among males, hepatic cancers accounted for a significantly larger percentage of cancer cases in the mountain vs. coastal origin group, while the reverse was true for penile cancer and KS. These preliminary data on cancer in Haiti are discussed with particular reference to dietary factors (for cancers of stomach, intestine, liver and cervix). The clarification and confirmation of these possible relationships between diet and cancer should provide an opportunity to elucidate environmental factors as causes of cancer.
New monoclonal antibodies specific for human sarcomas
Authors: Bruland Øyvind , Fodstad Øystein , Funderud Steinar , Pihl Alexander
Published: February 2007

Monoclonal antibodies (MAbs) against sarcoma‐associated cell membrane antigens were prepared by immunizing BALB/c mice with tumor cells from a human osteosarcoma, TPX, grown as a xenograft in athymic BALB/c nude mice. Spleen cells from immunized mice were hybridized with X‐63 Ag. 8.653 mouse myeloma cells which yielded 260 growing hybridomas. Seven of these produced antibodies that bound to TPX cells and to cells from another osteosarcoma, but not to autologous skin fibroblasts. MAbs from 2 (TP‐I and TP‐3) of these 7 clones did not cross‐react with non‐sarcomatous tumor cells or peripheral blood lymphocytes. Immunohistochemical studies on frozen tissue sections showed that the TP‐I (IgG‐2a) and TP‐3 (IgG‐2b) antibodies had characteristic and identical specificity profiles. Binding of TP‐I (TP‐3) was demonstrated to 15/15 (15/15) osteosarcomas, 3/3 (2/2) synovial sarcomas, 7/9 (6/8) malignant fibrous histiocytomas, 2/2 (1/1) malignant hemangiopericytomas, 1/2 (1/2) chondrosarcomas and 3/6 (1/3) unclassified sarcomas. The antibodies did not bind to any of 16 sarcomas belonging to other histological subtypes, including liposarcomas and leio‐and rhabdomyosarcomas. Moreover, they failed to bind to sections of 66 different non‐sarcomatous malignancies, or to any of a range of normal adult and fetal tissues, although some weak staining of proximal kidney tubules was seen. The restricted specificity of these antibodies to some major subtypes of human sarcomas makes them promising tools for identification and subclassification of sarcomas.
Increased incidence of IgA antibodies to the epstein‐barr virus‐associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia
Authors: Döucen Gottfried , Bross Klaus J. , Hecht Thomas , Brugger Wolfram , Löhr Georg W. , Hirsch Friedrich W.
Published: February 2007

Antibody liters to Epstein‐Barr virus (EBV)‐associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non‐Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti‐VGA IgG and anti‐EA IgG antibody liters. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy‐cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti‐VCA titers and 10 of these sera (21%) also contained IgA anti‐EA. The geometric mean titer (GMT) of IgA anti‐VCA was 2,510, the GMT of IgA anti‐EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B‐cell lymphomas are associated with EBV cannot be excluded.
Effects of a single dose of polychlorinated biphenyls to infant mice on N‐nitrosodimethylamine‐initiated lung and liver tumors
Authors: Anderson Lucy M. , Ward Jen‐Old M. , Fox Stephen D. , Isaaq Haleem J. , Riggs Charles W.
Published: February 2007

Polychlorinated biphenyls (PCBs) are widespread, chemically‐stable environmental contaminants; some congeners are commonly found in human adipose tissue and breast milk. We investigated the effects of a single dose of one PCB mixture (Aroclor 1254) on tumors initiated by N‐nitrosodimethylamine (NDMA), also a common environmental agent. Infant outbred Swiss male mice were treated with NDMA (5 mg/kg) i.p. on the 4th day of life, to initiate lung and liver tumors. Four days later each received a single intragastric dose of PCBs (50, 250, or 500 mg/kg of Aroclor 1254) or oil. Groups were killed 16 and 28 weeks later. At both endpoints the mice given 500 mg/kg PCBs after NDMA developed twice as many lung tumors (alveologenic adenomas) as those treated with NDMA only, a significant difference. The PCBs alone did not cause lung tumors. This is the first demonstration of tumor promotion by PCBs in an extrahepatic organ, and it occurred after a single exposure. There were also complex, multiple effects on NDMA‐caused liver tumors (adenomas and carcinomas) and on focal hepatocellular proliferative lesions: PCB treatment after the NDMA was associated with decreased number but increased size of these tumors and foci. All of these changes were accompanied by retention in the bodies of 0.1–6 ppm PCBs, as indicated by gas chromatography with electron capture detection. Of this, 80% or more consisted of 2,4,5, 2′,4′,5′‐and 2,3,4,2′,4′,5′‐hexachlorobiphenyls in about equal amounts for periods up to 28 weeks. These results point to a need for both experimental and epidemiological studies of the effect of PCB body burden on tumor development.
Prospective study on the relationship between cervical neoplasia and herpes simplex type 2 virus. III. Presence of herpes simplex type‐2 antibody in sera of subjects who developed cervical neoplasia later in the study
Authors: Krčmář M. , Suchánková A. , Kaňka J. , Vonka V.
Published: February 2007

Paired sera taken from 63 subjects who developed cervical neoplasia in the course of a prospective study on this disease were examined for the presence of herpes simplex virus type 2 (HSV‐2) antibody. The first serum was taken at enrolment into the study, while the second was obtained after development of the disease, i.e. 2–4 years later. Simultaneously, paired sera from a group of control subjects, who remained free of any cytological and colposcopical abnormalities throughout the study, were also investigated. Controls were matched with patients by age, age at first intercourse, number of sexual partners, smoking habits and history of diathermoelectrocoagulation ulation of ectopic epithelium and transformation zone of the cervix. The first sera from these subjects were obtained at enrolment while the second ones were taken at the end of the study, i.e. 5 to 7 years later. Antibody titers were remarkably stable in both patients and control subjects. Seroconversions from HSV‐2 negativity to HSV‐2 positivity as measured by the increase in the ll/l ratio or development of antibody reactive with HSV‐2‐specific glycoprotein G were rare and no significant dif‐ ferences between the patients and control subjects were detected. This indicates that the development of the disease was apparently not followed by immediate or early activation of latent HSV‐2 infection.
The stability of kidney‐induced selection of lewis lung tumor cell populations, and their metastasis‐related behavior
Authors: Weiss L. , Ward P. M. , Harlos J. P.
Published: February 2007

The surface charge densities of Lewis lung carcinoma (3LL) cells were measured in tumors transplanted into subcutaneous (s.c.) sites, and into the kidneys (K), as well as in kidney tumors transplanted to, and maintained in, the s.c. site (K.s.c.). K cells showed a significant increase in net negativity in comparison with s.c. cells, which was stable over 11 passages. On back‐transplantation of K cells to the s.c. site, the net negativity of K.s.c. cells was higher than that of the s.c. cells, but the increase was stable for only 7 passages; on subsequent passages the net negativity fell, approaching that of the s.c. cells. Detailed analyses suggest the presence in these tumors of 2 subpopulations of 3LL cells, whose proportions change in the different sites studied to produce changes in the mean electrophoretic mobilities of the whole cancer cell populations. The altered proportions of the 2 cell types in the 3 sites were not associated with major changes either in their general behavior with respect to metastasis, or in differential growth in various organs following s.c., tail vein, and left ventricular injections. Selection induced by growth in the kidney, as evidenced by physicochemical changes at the cancer cell surface, was not associated with kidney preference in metastasis or metastasis‐related behavior.
Characterization of the platelet‐aggregating activity of cancer cells with different metastatic potential
Authors: Grignani Guido , Pacchiarini Lucia , Almasio Piero , Pagliarino Mauro , Gamba Gabriella , Rizzo Salvatore Carlo , Ascari Edoardo
Published: February 2007

We studied the mechanisms of platelet activation by sublines exhibiting different metastatic potential of two murine experimental tumors: sublines M4 and M9 of the benzopyrene‐induced mFS6 sarcoma and sub‐ lines B77‐AA6 and B77–3T3 of RSV‐transformed BALB/c 3T3 fibroblasts. The neoplastic cells of both models induced platelet aggregation, secretion and prosta‐glandin biosynthesis. In the first model but not in the second, all these processes correlated with the in vivo malignancy of cells. Pretreatment of B77‐AA6 and B77–3T3 cells with apyrase significantly decreased platelet aggregation, while pretreatment of M4 cells was ineffective. However, pretreatment with trypsin or neuraminidase was effective in reducing platelet aggregation induced by M4 cells, but not that induced by any of the others; furthermore, phospholipase A2 reduced the platelet response by all sublines. Finally, platelet‐activating activity was also found in the pellets obtained following centrifugation of culture media. These results suggest that platelets are stimulated by cancer cells through different mechanisms; platelet activation by a sialo‐lipo‐protein complex of the cellular membrane was found to be characteristic of the model in which the platelet‐aggregating activity of neoplastic cells correlated with their in vivo metastatic behavior.
Aspartate‐assisted immune stimulation: Its importance in antitumor and antiviral protection
Authors: Chany Charles , Cerutti Italina
Published: February 2007

Immune stimulators such as Cornyebacterium paryum (CP) are useful for antitumoral and antiviral therapy. However, the immune trigger cannot be reactivated without adversely affecting the disease. We have tried to amplify the results yielded by a single injection of CP by using either interleukin‐2 (1L.2) or aspartate salts (ASP). In the present report, we show that 1L2 has no detectable clinical effect. In contrast, the addition of an ASP salt increases the antiviral and antitumoral protection afforded by the CP‐induced trigger. Moreover, treatment using only ASP slightly protects against tumor development and significantly increases antiviral resistance during experimental encephalomyocarditis (EMC) infection. This ASP‐assisted CP immune stimulation improves antitumoral resistance even when ascitic tumors have already developed. In the latter case, tumor regression can even be detected. Since ASP increases T‐cell cytotoxicity in vitro and aggravates spontaneous T‐cell lymphomas in AKR mice, the involvement of T‐cell‐mediated immunity may explain antitumoral and antiviral effects. We propose the use of this therapeutic model for human cancer therapy, and possibly for treating AIDS.
Effect of Fluosol‐DA/O2 on tumor‐cell and bone‐marrow cytotoxicity of nitrosoureas in mice bearing FSA‐II fibrosarcoma
Authors: Teicher Beverly A. , Holden Sylvia A. , Rose Christopher M.
Published: February 2007

The perfluorochemical emulsion, Fluosol‐DA, combined with carbogen breathing, potentiates the effects of radiation and a number of chemotherapeutic agents in several rodent tumors. The interaction of Fluosol‐DA with drugs may be quite complex. In addition to increasing the oxygen supply in the tumor, Fluosol‐DA may alter the pharmacokinetics of the drug and function as a drug delivery system. A series of 4 nitrosoureas of varying lipophilicity were administered as single doses intravenously (i.v.) to C3H/Be/FeJ mice bearing subcutaneous FSa‐11C fibro sarcomas. Doses of 40 mg/kg of CCNU, 15 mg/kg of BCNU, 20 mg/kg of MeCCNU and 15 mg/kg of chlorozoticin followed by 2 hr of breathing 95% oxygen produced tumor growth delays of 7.5, 4.0, 3.8 and 2.7 days, respectively. When the drug injection was followed immediately by 0.3 ml of Fluosol‐DA and 2 hr of breathing 95% oxygen, the tumor growth delay produced by CCNU, BCNU, MeCCNU and chlorozoticin increased 2‐fold, 10‐fold, 4.5‐fold and 3.5‐fold, respectively. Administration of the drugs in Fluosol‐DA followed by 2 hr of 95% oxygen breathing resulted in a 3.5‐fold increase in tumor growth delay with CCNU, a 17‐fold increase with BCNU, a 12.5‐fold increase with MeCCNU and a 6‐fold increase with chlorozoticin compared to drug and 95% oxygen breathing. These results are quantified in terms of cell survival by the tumor excision assay. Effects on the bone marrow from each treatment were measured using the granulocyte‐monocyte colony‐forming units (CFU‐GM) assay. There was no correlation between the lipophilicity of the nitro sources tested and the tumor growth delay produced by each treatment.
The immune system during the pre‐cancer and the early cancer period. IL‐2 production by PBL from post‐menopausal women with and without endometrial carcinoma
Authors: Yron I. , Schickler M. , Fisch B. , Pinkas H. , Ovadia J. , Witz I. P.
Published: February 2007

We report on alterations in IL‐2 production and cell proliferation following PHA stimulation of peripheral blood lymphocytes (PBL) from stage‐1 endometrial carcinoma (EC) patients, and on mechanisms involved in these alterations. Our study includes 3 groups: EC patients, post‐menopausal women at high risk of developing EC, and age‐matched healthy women. IL‐2 production was markedly lower in most EC patients than in healthy controls. Varying levels of IL‐2 were produced by PBL from women in the high‐risk group. The proliferative response of PBL to PHA appeared to correlate with levels of IL‐2 production. Our results suggest that macrophages are involved, in part, in the modulation of T‐cell functions of EC patients.
S‐phase fraction of human brain tumors in situ measured by uptake of bromodeoxyuridine
Authors: Hoshino Takao , Nagashima Tadashi , Cho Kyung G. , Murovic Judith A. , Hodes Jonathan E. , Wilson Charles B. , Edwards Michael S. B. , Pitts Lawrence H.
Published: February 2007

One hundred fifty‐four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S‐phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR‐labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1 %, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Non‐ malignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well‐defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.
Effects of mouse interferon on human tumour xenografts in the nude mouse host
Authors: Balkwill F. R. , Proietti E.
Published: February 2007

Murine interferon (IFN) inhibited the growth of 3/3 human tumour xenografts growing in nude mice. This inhibition was independent of the sensitivity of the xenograft to human IFN. In contrast to human IFN, the murine IFN did not directly affect the human tumour cells in vitro as measured by levels of the IFN‐ induced enzyme 2–5A synthetase or elevation of HLA expression. In preliminary investigations into the role of the host in the murine IFN‐mediated tumour inhibition, we found equal activities of this IFN in nude and in beige (NK‐deficient) nude mice. Moreover, murine IFN did not elevate levels of NK‐cell activity in either of these mouse strains. We conclude that murine IFN mediates this tumour inhibition via an effect on the tumour‐bearing host that may or may not involve immune mechanisms.
Recombinant human interferon gamma suppresses HTLV‐III replication in vitro
Authors: Nakashima Hideki , Yoshida Tsutomu , Harada Shinji , Yamamoto Naoki
Published: February 2007

Effect of human interferon gamma (rINF‐γ) on HTLV‐III replication was evaluated quantitatively via a novel infection system using HTLV‐I‐carrying MT‐4 cells. Treatment of HTLV‐III‐infected MT‐4 cells with different concentrations (1–1,000 U/ml) of rINF‐γ, which did not affect the growth or viability of uninfected cells, significantly blocked the appearance of immunofluorescent antigens of HTLV‐III and the virus‐induced cytopathic effect in a dose‐dependent manner. A plaque assay was applied to measure the exact amount of viral particles released from HTLV‐III‐infected MT‐4 cultures either untreated or treated with rINFγ after infection. The number of plaques per dish decreased with increasing drug concentrations. About 50% and 80% of HTLV‐III replication were inhibited by the addition of 100 and 1,000 U/ml of rINF‐γ, respectively. The effects of INF were observed by day 5 of incubation with the chemical. However, longer treatment of cells with rINFγ permitted a gradual increase in viral replication. Re‐addition of fresh INF into cultures did not change this pattern significantly.
Early spontaneous metastasis in the human epidermoid carcinoma HEp3/Chick embryo model: Contribution of incidental colonization
Authors: Gordon Joseph R. , Quigley James P.
Published: February 2007

In the experimental model system where human tumor cells (HEp3) are implanted on the chorioallantoic membrane (CAM) of the chick embryo, metastasis of HEp3 cells to the embryonic lung occurs within a few days. Such rapidity in tumor dissemination makes this an attractive and potentially useful model for studying the metastatic process. The model, however, involves microvascular trauma at the site of implantation and thus tumor cells may accidentally enter the circulation during implantation or shortly thereafter. If these cells are the cause of the lung metastasis subsequently measured, the model would be in effect a colonization system and not a true, spontaneous metastasis system. The possible contribution of accidental lung colonization to secondary tumor growth was therefore critically examined in this model. In standard metastasis assays, HEp3 was inoculated onto the CAMs of 10‐day embryos, which were then incubated for various periods of time. The embryos' lungs were passaged to a second group of CAMs, incubated for 7 days to allow expansion of any HEp3 cells present, and then assayed for HEp3 cells by both microscopy and measurement of human plasminogen activator (PA) activity. Metastasis was evidenced by PA values above background (30mU/mg protein). Morphological analysis of HEp3 cells in the embryonic lung correlated closely with PA values. To focus on the early stages of tumor dissemination when colonization might occur, the primary tumor was surgically excised from 38 embryos at various intervals after tumor inoculation, and after the operation embryos were allowed to develop to day 17. This procedure increased estimated assay sensitivity down to the level of 1 to 10 cells per lung in embryos operated on within 2 days of inoculation. Median PA values in the transplanted lungs were 13, 3, 37, 1,290 and 3,765 mil/mg protein in the groups operated on at 4 hr, 1, 2, 3 and 4 days after inoculation, respectively. Thus very few or no HEp3 cells arrest and grow in the lungs during the first 24 to 48 hr, but extensive metastasis occurs by 72–96 hr. Accidental colonization therefore plays no major part in the rapid pulmonary spread of HEp3 in this model.
Expression of HLA‐D sub‐region products on human colorectal carcinoma
Authors: Ghosh A. K. , Moore M. , Street A. J. , Howat J. M. T. , Schofield P. P.
Published: February 2007

The major histocompatibility complex (MHC) status of normal, inflamed, pre‐malignant and malignant epithelia of the human gastrointestinal tract was investigated by immunocytochemical methods using monoclonal antibodies (MAbs) directed against heavy (α)‐and light (β2m)‐chain Class‐I molecules and sub‐locus products (DP, DQ, DR) of the HLA‐D region. Class‐I expression on epithelial cells appeared to vary little with pathological status except in the case of 4/32 (13%) colorectal carcinomas in which the antigens were undetectable or scanty. The pattern of Class‐II expression was more complex. The antigens were readily detectable on normal stomach epithelium, in villous adenomas and in inflammatory bowel mucosa. In each of these situations DR was the predominant specificity, followed by DP and DQ. Expression on normal colonic epithelium was usually negative but, in the vicinity of a neoplasm or an area of marked leukocyte infiltration, Class‐II molecules (DR>DP>DQ) were detectable. A similar pattern of non‐coordinate expression was found on 23/32 (72%) colorectal carcinomas, but on the remaining 28% no Class‐II products were detectable, under conditions wherein stromal leukocytes were strongly stained. The data suggest that In a significant proportion (nearly 30%) of primary colorectal carcinomas, the capacity for Class‐II induction, a constitutive or acquired feature of normal colorectal epithelium, is either diminished or lost. Also, tumor Class‐II status is not correlated to Dukes' stage or differentiation.
Imbalance of sex chromosomes, with gain of early‐replicating X, in human solid tumors
Authors: Dutrillaux B. , Muleris M. , Seureau M. Gerbault
Published: February 2007

An imbalance of sex chromosomes was observed in several cases of solid tumors: colorectal, anal canal and breast carcinomas. Replication studies, using BUdR incorporation, show that in males there is a tendency towards a gain of early‐replicating X and a deficiency of Y chromosomes. In females, there is a tendency towards a gain of early‐replicating X and a loss of late‐replicating X chromosomes. Although almost no replication studies have been published in the literature, making it impossible to distinguish between late‐and early‐replicating Xs, it is likely that a similar situation exists for several solid tumors other than those we have studied. A possible consequence of this imbalance is briefly discussed.