International Journal of Cancer
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Identification of five chromosomal regions involved in predisposition to melanoma by genome‐wide scan in the MeLiM swine model Abstract In human familial melanoma, 3 risk susceptibility genes are already known, CDKN2A , CDK4 and MC1R . However, various observations suggest that other melanoma susceptibility genes have not yet been identified. To search for new susceptibility loci, we used the MeLiM swine as an animal model of hereditary melanoma to perform a genome scan for linkage to melanoma. Founders of the affected MeLiM stock were crossed with each other and with healthy Duroc pigs, generating MeLiM, F1 and backcross families. As we had previously excluded the MeLiM CDKN2A gene, we paid special attention to CDK4 and MC1R , as well as to other candidates such as BRAF and the SLA complex, mapping them on the swine radiation hybrid map and/or isolating close microsatellite markers to introduce them into the genome scan. The results revealed, first, that swine melanoma was inherited as an autosomal dominant trait with incomplete penetrance, preferably in black animals. Second, 4 chromosomal regions potentially involved in melanoma susceptibility were identified on Sus Scrofa chromosomes (SSC) 1, 2, 7 and 8, respectively, in intervals 44–103, 1.9–18, 59–73 and 47–62 cM. A fifth region close to MC1R was revealed on SSC 6 by analyzing an individual marker located at position 7.5 cM. Lastly, CDK4 and BRAF were unlikely to be melanoma susceptibility genes in the MeLiM swine model. The 3 regions on SSC 1, 6 and 7, respectively, have counterparts on human chromosomes (HSA) 9p, 16q and 6p, harboring melanoma candidate loci. The 2 others, on SSC 2 and 8, have counterparts on HSA 11 and 4, which might therefore be of interest for human studies. © 2004 Wiley‐Liss, Inc.
International Journal of Cancer - Tập 110 Số 1 - Trang 39-50 - 2004
A pigmentation‐associated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum Abstract Antibodies in the serum of melanoma patient AU precipitate an antigen from 125 I‐labelled extracts of cultured autologous melanoma cells. The antigen, which is probably not a cell surface component, is present in other pigmented melanomas but not in non‐pigmented melanomas or other tumor cell types, and the amount of antigen is correlated with the degree of pigmentation. These conclusions are based on absorption experiments with 11 pigmented melanomas, 8 non‐pigmented melanomas, 3 astrocytomas, 12 carcinomas of various histological types, 1 leukemia, 2 EB‐virus‐transformed B lymphocyte lines, and human erythrocytes. The antigen was also detected in cultured human melanocytes. It has a molecular weight of 70,000, an isoelectric point of pH 5.3, and it binds to concanavalin A‐Sepharose. Ninety‐six sera from other melanoma patients were examined and none of them precipitated this antigen. As described previously, the serum from patient AU also has antibodies to a unique (Class 1) tumor antigen found only on AU melanoma cells. The pigmentation‐associated, differentiation antigen and the unique antigen are clearly different in their distribution, but some relationship between these unusual antibody responses is possible.
International Journal of Cancer - Tập 32 Số 6 - Trang 717-721 - 1983
<scp>M</scp>aternal residential pesticide use and risk of childhood leukemia in <scp>C</scp>osta <scp>R</scp>ica Evidence suggests that early‐life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self‐reported maternal residential pesticide use and nearby pesticide applications–before and after child's birth–were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population‐based case‐control study (2001‐2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were identified through the Costa Rican Cancer Registry and National Children's Hospital. Population controls (n = 577) were drawn from the National Birth Registry. We fitted unconditional logistic regression models adjusted for child sex, birth year, and socioeconomic status to estimate the exposure‐outcome associations and also stratified by child sex. We observed that self‐reported maternal insecticide use inside the home in the year before pregnancy, during pregnancy, and while breastfeeding was associated with increased odds of ALL among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]: 1.05–2.53), 1.75 (1.13–2.73), and 1.75 (1.12–2.73), respectively. We also found evidence of exposure‐response relationships between more frequent maternal insecticide use inside the home and increased odds of ALL among boys and girls combined. Maternal report of pesticide applications on farms or companies near the home during pregnancy and at any time period were also associated with ALL. Our study in Costa Rica highlights the need for education to minimize pesticide exposures inside and around the home, particularly during pregnancy and breastfeeding.
International Journal of Cancer - Tập 143 Số 6 - Trang 1295-1304 - 2018
Therapeutic effect of adriamycin encapsulated in long‐circulating liposomes on meth‐a‐sarcoma‐bearing mice Abstract Long‐circulating liposomes modified with a uronic‐acid derivative, palmityl‐D‐glucuronide (PGIcUA), have been developed previously for the passive targeting of liposomes to tumor tissues. In this study, we examined the therapeutic effect of adriamycin (ADM) encapsulated in PGIcUA liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and PGIcUA (molar ratio, 40/40/10) since this amount of PGIcUA was enough to endow liposomes with long‐circulating activity. Long‐circulating activity was also observed with palmityl‐D‐galacturonide (PGalUA) modified liposomes, suggesting that uronic acid plays an important role in preventing liposomes from being trapped in the reticuloendothelial system (RES). ADM was loaded in liposomes by a remote‐loading method. Free or liposomal ADM was injected i.v. into BALB/c mice bearing s.c.‐implanted Meth‐A sarcoma. The liposomal formulation was efficient for reducing tumors, prolonging survival time and curing the animals, especially in the case of large tumors where free ADM was not. Furthermore, PGIcUA liposomes were more effective than conventional liposomes containing dipalmitoylphosphatidylglycerol (DPPG) instead of PGIcUA for prolonging survival time in mire. It might therefore be appropriate to use PGIcUA liposomes as the carriers of anticancer drugs.
International Journal of Cancer - Tập 58 Số 3 - Trang 415-419 - 1994
Formation of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal‐modified proteins in human renal‐cell carcinoma Abstract To study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal‐cell carcinoma (RCC), we analvzed 35 cases of RCC for 2 parameters of oxidative damage: 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a mutation‐prone DNA‐ base ‐modified product, was measured by means of high‐performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4‐hydroxy‐2‐nonenal (HNE)‐modified proteins were measured with a poly‐clonal antibody against HNE‐modified proteins. A 54% higher content of 8‐OHdG was found in RCC than in the corresponding non‐tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non‐tumorous kidneys. Immunohistochemistry for HNE‐modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non‐tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.
International Journal of Cancer - Tập 58 Số 6 - Trang 825-829 - 1994
Biochemical characterization of human carcinoma surface antigen associated with protein kinase activity Abstract MAb 50H.19 immunoprecipitates two proteins from lysates of human carcinoma cell lines, and embryonic fibroblasts intrinsically labelled with 3 H‐leucine, 35 S‐methionine, or a 3 H‐amino acid mixture; a major component of M, = 22,000 (22 kd component) and a minor component of M, = 24,000 (24 kd component). Oligomeric forms of the proteins are not observed under reducing or non‐reducing conditions. Both proteins are expressed on the plasma membrane, and are glycoproteins. We investigated the relationship between the proteins in terms of their glycosylation and derivation from precursors. The 22 kd component is O‐glycosylated as demonstrated by 3 H‐galactose incorporation, insensitivity to tunicamycin (TM), and its stepwise generation from a 20.5 kd precursor. The 24 kd protein is N‐glycosylated, as shown by 3 H‐mannose incorporation, and by the total inhibition of its synthesis in the presence of TM. Further evidence for its N‐glycosylation is provided by the appearance of a 23 kd precursor in lysates from the osteogenic sarcoma cell line SKOSC pulse‐labelled for 5 min, a time preceding O‐glycosylation of the 20.5 kd protein. Furthermore, mild alkali treatment of the immune complex leads to a loss of approximately 1,000 daltons in each glycoprotein confirming the O‐glycosylated nature of the 22 kd component, and suggesting that the 24 kd component is additionally O‐glycosylated. Both glycoproteins undergo an apparent increase of molecular weight of about 500 daltons when run in the non‐reduced form on SDS polyacrylamide gels under standard electrophoretic conditions, suggesting they contain a similar degree of intra‐chain disulphide bonding. Confirmatory evidence that the two components share a common polypeptide backbone is provided by the appearance of only the 20.5 kd component in lysates from SKOSC cells pulse‐labelled for 5 min in the presence of TM.
International Journal of Cancer - Tập 34 Số 6 - Trang 821-829 - 1984
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 Abstract Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high‐resource countries. Striking differences in the patterns of cancer from region to region are observed.
International Journal of Cancer - Tập 127 Số 12 - Trang 2893-2917 - 2010
Aberrant expression of nuclear vimentin and related epithelial–mesenchymal transition markers in nasopharyngeal carcinoma Abstract Expression of vimentin and the epithelial to mesenchymal transition (EMT) markers E‐cadherin, β‐catenin is essential for the progression of various human cancers. Our study aimed to investigate the aberrant localization E‐cadherin, β‐catenin and vimentin, and their prognostic significance in 122 nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. Our results showed that both membranous and cytoplasmic localization of E‐cadherin staining were associated with lymph node metastasis (p = 0.000 and 0.005, respectively) and clinical stage (p = 0.000 and 0.007, respectively). High cytoplasmic β‐catenin correlated significantly with larger tumor size (p = 0.020), lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.036). However, no significant difference was observed between membranous β‐catenin and clinicopathologic features (p ≥ 0.05). High nuclear vimentin expression correlated significantly with positive lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Multivariate analysis showed that nuclear vimentin and cytoplasmic E‐cadherin were independent prognostic factors (p = 0.016 and 0.001, respectively), as well as M classification (p = 0.001). More importantly, patients with high coexpression of nuclear vimentin and cytoplasmic E‐cadherin had shorter survival time (p = 0.000). Furthermore, high coexpression of these two proteins was closely associated with lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Our studies provide convincing evidence that EMT may play an important role in the biological progression of NPC, and nuclear vimentin and cytoplasmic E‐cadherin might have independent prognostic value in NPC patients and serve as novel targets for prognostic therapeutics.
International Journal of Cancer - Tập 131 Số 8 - Trang 1863-1873 - 2012
HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression Abstract The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)‐E/β2m on tumor cells. The inhibitory effect of HLA‐E/β2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA‐E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ , in a series of 80 CRC (i ) the HLA‐E and β2m coexpression by tumor cells, (ii ) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial tumor‐infiltrating lymphocyte (IEL‐TIL) and (iii ) the expression of CD94/NKG2 receptor on IEL‐TIL. These data were then correlated to patient survival. We provided (i ) the in situ demonstration of HLA‐E/β2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii ) the significant association between HLA‐E/β2m overexpression by tumor cells and increased density of CD8+ cytotoxic, CD244+ and CD94+ IEL‐TIL and (iii ) finally, the unfavorable prognosis associated with HLA‐E/β2m overexpression by tumor cells. Our findings show that HLA‐E/β2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL‐TIL.
International Journal of Cancer - Tập 131 Số 4 - Trang 855-863 - 2012
The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015 Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X‐rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR‐associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.
International Journal of Cancer - Tập 144 Số 12 - Trang 2954-2963 - 2019
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