International Journal of Cancer
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Identification of cancer/testis genes by database mining and mRNA expression analysis Abstract Cancer/testis (CT) antigens are immunogenic proteins expressed predominantly in gametogenic tissue and cancer; they are considered promising target molecules for cancer vaccines. The identification of new CT genes is essential to the development of polyvalent cancer vaccines designed to overcome tumor heterogeneity and antigen loss. In the current study, a search for new CT genes was conducted by mining the Unigene database for gene clusters that contain expressed sequence tags derived solely from both normal testis and tumor‐derived cDNA libraries. This search identified 1,325 different cancer/testis‐associated Unigene clusters. The mRNA expression pattern of 73 cancer/testis‐associated Unigene clusters was assessed by reverse transcriptase polymerase chain reaction. Three gene products, CT15/Hs.177959, CT16/Hs.245431 and CT17/Hs.178062, were detected only in testis and in tumor tissue. CT15 is equivalent to ADAM2/fertilin‐β. CT16, an uncharacterized gene product, has homology (30–50%) to members of the GAGE gene family and is 89% identical to CT16.2/Hs.293317, indicating that CT16 and CT16.2 are members of a new GAGE gene family. The uncharacterized gene product, CT17, has homology (30%) to phospholipase A1. RT‐PCR analysis showed that CT15 is expressed exclusively in renal cancer, whereas CT16 and CT17 are expressed in a range of human cancers. Real‐time RT‐PCR analysis of newly defined CT genes and the prototype CT antigens, MAGE‐3 and NY‐ESO‐1, revealed low levels (less than 3% of the level detected in testis) of CT15, CT16 and NY‐ESO‐1 in a limited range of normal, non‐gametogenic tissues. This study demonstrates the merits of database mining with respect to the identification of tissue‐restricted gene products expressed in cancer. © 2002 Wiley‐Liss, Inc.
International Journal of Cancer - Tập 98 Số 4 - Trang 485-492 - 2002
The Danish case‐control study of cutaneous malignant melanoma. I. Importance of host factors Abstract The relationshop between cutaneous malignant melanoma and possible host factors was Investigated in a populationbased case‐control study from East Denmark over a 3‐year period. A total of 474 melanoma patlents and 926 population controls aged 20–79 years were interviewed. Patients with lentigo maligna melanoma were not included. The major constitutional risk factors were: number of raised naevi on the arms (RR = 5,1 for 5+ vs, none), degree of freckling (RR = 2.9 for many vs, none), and light hair colour (RR = 1.7 for blond/fair vs. dark brown/black), which were independent of one another. An apparent synergy between number of raised naevi on the arms and degree of freckling was found. Thus, persons at high risk of melanoma may be identified by a simple assessment of naevi and degree of freckling. No significent difference was found between superficial spreading melanoma and nodular melanoma with regard to the most important host factors.
International Journal of Cancer - Tập 42 Số 2 - Trang 200-206 - 1988
An analysis of trends in mortality from malignant melanoma of the skin in Australia Abstract Australian mortality rates from cutaneous malignant melanoma in successive periods from 1931 to 1977 have been examined with respect to geographic variation and trend with time and birth cohort. The age‐standardized rates rose from 0.8/100,000 in males and 0.6/100,000 in females in 1931–34 to 4.2/100,000 and 2.5/100,000 in 1975–77. Mortality rates were highest in Queensland in the north of Australia and diminished on a gradient from the north to south of the country. An analysis designed to separate effects due to calendar year, birth cohort and age showed that virtually all the secular trend in rates could be explained by increases in successive birth cohorts, beginning as early as 1865 and stabilizing with the cohorts born around 1925 in women and 1935 in men. It is suggested that the cohort‐based increase in mortality resulted from life‐style changes occurring with successive generations. Its stabilization in recent birth cohorts, if persistent, suggests that the secular trend towards increasing total mortality from melanoma will also stabilize over the next 40 years.
International Journal of Cancer - Tập 26 Số 6 - Trang 703-709 - 1980
Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer
International Journal of Cancer - Tập 140 Số 3 - Trang 611-617 - 2017
EGFR‐TKIs plus local therapy demonstrated survival benefit than EGFR‐TKIs alone in EGFR‐mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases To investigate whether addition of local therapy to EGFR‐TKIs could provide survival benefit than EGFR‐TKIs alone in EGFR‐mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR‐mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression‐free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs . 8.6 m, p <0.001) and OS (31.2 vs . 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR‐TKIs and 23 received EGFR‐TKIs plus local therapy as first‐line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs . 7.9 m, p = 0.041) and OS (36.8 vs . 21.3 m, p = 0.034) than EGFR‐TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR‐TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs . 9.2 m, p = 0.007) and OS (28.3 vs . 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR‐TKIs plus local therapy showed prolonged survival benefit than EGFR‐TKIs alone in EGFR‐mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario.
International Journal of Cancer - Tập 144 Số 10 - Trang 2605-2612 - 2019
The proto‐oncogene/translation factor eIF4E: A survey of its expression in breast carcinomas Abstract The eukaryotic translation initiation factor elF‐4E binds to the cap structure of mRNAs as one component of the elF‐4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of elF‐4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth‐control gene products which are normally translationally repressed. Whereas the mechanism of elF‐4E‐mediated transformation is being actively pursued, clinical investigations into the expression of elF‐4E in prevalent human cancers are lacking. We have recently initiated a screen of breast carcinomas by probing with elF‐4E antiserum. Using Western blots, we have analyzed the level of elF‐4E in 38 carcinomas, 7 normal samples and 3 fibroadenomas. We found that elF‐4E was elevated 3‐ to 10‐fold in virtually all the carcinomas we analyzed, but not in fibroadenomas. This analysis was also confirmed by immunohistological staining in situ , showing that overexpression of elF‐4E can be readily identified at the single‐cell level. Our results suggest that an elevation of elF‐4E may be an essential component in the development of breast cancer. © 1995 Wiley‐Liss, Inc.
International Journal of Cancer - Tập 64 Số 1 - Trang 27-31 - 1995
The increase in working years due to elimination of cancer as a cause of death Abstract The relative significance of various forms of cancer in terms of causing death is analysed by estimation of the increase in person‐years of working age (20‐64 years) following elimination of the disease. Methods based upon the theory of competing risks are applied to the statistics on causes of death in Finland during the years 1966‐70. It is estimated that if there were no lung cancer (the commonest type of cancer in both morbidity and mortality statistics in males in Finland) the annual deaths saved would yield 5,900 working years (both sexes combined). Leukaemia and cancer of the stomach would be next in rank order, with figures of respectively 4,000 and 3,900 working years more. Female cancer with the highest incidence, that of the breast, would be characterized by 2,900 additional working years. The significance of types of cancer that affect young people is stressed in these calculations: leukaemia, brain tumours and lymphomas (both sexes combined) are 6th, 12th and 11th respectively in the statistics of cancer causes of death, but 2nd, 4th and 6th respectively in the list of additional working years to be gained by elimination of the disease. On the other hand, cancer of the prostate, 3rd in males according to the annual numbers of cancer deaths, would take the 15th position for the increase in working years in males. If no risk of cancer existed, the annual deaths saved would produce 36,000 working years, a figure exceeded only by those for cardiovascular diseases (55,000 working years) and accidents (51,000 working years). The results indicate that no practical differences exist between the results derived under the assumptions of various models for competing risks, but that the exclusion of competing risks may result in considerable degrees of bias in estimation if the population has a high general mortality.
International Journal of Cancer - Tập 17 Số 4 - Trang 429-435 - 1976
International trends and patterns of primary liver cancer
International Journal of Cancer - Tập 94 Số 2 - Trang 290-296 - 2001
Functional coexpression of Interleukin (IL)‐7 and its receptor (IL‐7R) on Hodgkin and Reed‐Sternberg cells: Involvement of IL‐7 in tumor cell growth and microenvironmental interactions of Hodgkin's lymphoma Abstract The clinical and pathological features of classical Hodgkin lymphoma (cHL) mirror an abnormal tissue and systemic immune response due to the production of a variety of cytokines and chemokines by the malignant Hodgkin‐Reed‐Sternberg (H‐RS) cells and/or surrounding reactive cells. Here, we demonstrate that HL‐derived cell lines (L‐428, KM‐H2, HDLM‐2, L‐1236 and L‐540) and primary H‐RS cells from lymph node tissues of HL patients express the IL‐7(R) receptor. IL‐7 appears to be involved in autocrine circuitries of HL because L‐1236, HDLM‐2 and KM‐H2 cells display the constitutive production of IL‐7 and neutralizing anti‐IL‐7 antibodies induces a statistically significant inhibition of their basal proliferation. In addition, IL‐7, either exogenous or fibroblasts‐derived, promotes the clonogenic growth and reduces apoptosis of cultured H‐RS cells, being also able to partially protect these cells from the cytotoxic effects of doxorubicin. We also provide evidence that IL‐7 stimulates IL‐6 secretion from IL‐7R‐expressing fibroblasts from HL‐involved lymph nodes (HLFs), and that a striking increase in IL‐6 secretion can be observed in cocultures of HLFs with L1236 cells. Finally, we show that L‐1236 cells‐derived IL‐7 represents a costimulator for proliferation of purified CD4+CD25+CD127dim/− regulatory T cells (Tregs). Taken together, our data indicates that the IL‐7/IL‐7R axis constitutes an additional signaling pathway between H‐RS cells and their reactive cellular background, thereby affecting proliferation and survival of tumor cells, acting as a cofactor for Tregs expansion and enhancing the microenviromental production of IL‐6, a cytokine associated with the presence of “B” symptoms and a poor outcome in HL patients. © 2009 UICC
International Journal of Cancer - Tập 125 Số 5 - Trang 1092-1101 - 2009
Enhancement of the antiproliferative effect of <i>cis</i>‐diamminedichloroplatinum(II) and nitrogen mustard by inhibitors of protein kinase C Abstract Quercetin (3, 3′, 4′, 5, 7‐pentahydroxyflavone) has been shown to inhibit a variety of enzymes including the calcium‐ and phospholipid‐dependent protein kinase (protein kinase C) in vivo and in vitro . We show that this compound synergistically enhances the antiproliferative activity of cis ‐diamminedichlo‐roplatinum(II) (cis ‐DDP) and nitrogen mustard. Quercetin does not affect the repair of DNA interstrand cross‐links introduced by cis ‐DDP. Long‐term exposure to 12‐O ‐tetradeca‐noylphorbol‐13‐acetate (TPA), which reduces total protein kinase C activity, also amplifies the growth‐inhibitory effect of cis ‐DDP and acts synergistically with quercetin. A synergism is also observed if tamoxifen or staurosporine are combined with cis ‐DDP. For both drugs the dose‐effect curves for the inhibition of protein kinase C closely resemble the dose‐effect curves for the antiproliferative activities. Although alternative mechanisms cannot be definitively excluded, the effects of quercetin, TPA, tamoxifen and staurosporine may result from the inhibition of protein kinase C.
International Journal of Cancer - Tập 42 Số 3 - Trang 382-388 - 1988
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