Showing papers on "Cancer published in 2002"
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
Abstract: Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.
9,664 citations
TL;DR: Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy and could help to improve the treatment of metastatic disease.
Abstract: Metastases, rather than primary tumours, are responsible for most cancer deaths. To prevent these deaths, improved ways to treat metastatic disease are needed. Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cells will grow there. Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy.
3,810 citations
TL;DR: Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago and DNA of specific HPV types has since been found in almost all cervical cancer biopsies.
Abstract: Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago. DNA of specific HPV types has since been found in almost all cervical cancer biopsies. HPV oncogenes that are expressed in these cells are involved in their transformation and immortalization, and are required for the progression towards malignancy. Epidemiological studies have underlined that HPVs are the main aetiological factor for cervical cancer. But how has this knowledge been translated into the clinic to allow the prevention, screening and treatment of cervical cancer?
3,610 citations
TL;DR: A bioinformatics tool was developed and used to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the ovary, justifying a prospective population-based assessment of proteomic pattern technology as a screening tool for all stages of ovarian cancer in high-risk and general populations.
3,144 citations
TL;DR: The American Cancer Society estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival, using National Cancer Institute (NCI) incidence and National Center for Health Statistics (NCHS) mortality data as mentioned in this paper.
Abstract: Every year the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival, using National Cancer Institute (NCI) incidence and National Center for Health Statistics (NCHS) mortality data. Incidence and death rates are age adjusted to the 1970 US standard population. It is estimated that 1,284,900 new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. From 1992 to 1998, cancer death rates declined in males and females, while cancer incidence rates decreased among males and increased slightly among females. Most notably, African-American men showed the largest decline for both incidence and mortality. Nevertheless, African Americans still carry the highest burden of cancer with later-stage cancer diagnosis and poorer survival compared with whites. Despite the continued decline in cancer death rates, the total number of recorded cancer deaths in the United States continues to increase slightly due to the aging and expanding population.
2,964 citations
TL;DR: The adoptive transfer of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen resulted in the persistent clonal repopulation of T cells in cancer patients, leading to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction.
Abstract: We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.
2,828 citations
TL;DR: Dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.
Abstract: Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.
2,566 citations
TL;DR: The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anti-cancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance as mentioned in this paper.
Abstract: The design of cancer chemotherapy has become increasingly sophisticated, yet there is no cancer treatment that is 100% effective against disseminated cancer. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Frequently resistance is intrinsic to the cancer, but as therapy becomes more and more effective, acquired resistance has also become common. The most common reason for acquisition of resistance to a broad range of anticancer drugs is expression of one or more energy-dependent transporters that detect and eject anticancer drugs from cells, but other mechanisms of resistance including insensitivity to drug-induced apoptosis and induction of drug-detoxifying mechanisms probably play an important role in acquired anticancer drug resistance. Studies on mechanisms of cancer drug resistance have yielded important information about how to circumvent this resistance to improve cancer chemotherapy and have implications for pharmacokinetics of many commonly used drugs.
2,429 citations
TL;DR: Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.
2,281 citations
TL;DR: The use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients and show antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor and to a markedly inhibited response ofascular endothelial cells to stimulation by VEGF.
Abstract: Conventional immunosuppressive drugs have been used effectively to prevent immunologic rejection in organ transplantation. Individuals taking these drugs are at risk, however, for the development and recurrence of cancer. In the present study we show that the new immunosuppressive drug rapamycin (RAPA) may reduce the risk of cancer development while simultaneously providing effective immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses of RAPA effectively controlled the growth of established tumors. In contrast, the most widely recognized immunosuppressive drug, cyclosporine, promoted tumor growth. From a mechanistic perspective, RAPA showed antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients.
1,701 citations
TL;DR: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women, and SHBG was associated with a decrease in Breast cancer risk.
Abstract: Background: Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women Methods: We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case–control sets matched within each study Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate Results: The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 142 (95% confidence interval [CI] = 104 to 195), 121 (95% CI = 089 to 166), 180 (95% CI = 133 to 243), and 200 (95% CI = 147 to 271; Ptrend<001); the RRs for women with increasing quintiles of free estradiol were 138 (95% CI = 094 to 203), 184 (95% CI = 124 to 274), 224 (95% CI = 153 to 327), and 258 (95% CI = 176 to 378; Ptrend<001) The magnitudes of risk associated with the other estrogens and with the androgens were similar SHBG was associated with a decrease in breast cancer risk (P trend = 041) The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis Conclusion: Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women [J Natl Cancer Inst 2002;94:606–16]
TL;DR: Melanoma and non‐melanoma (basal and squamous cell carcinoma) skin cancer (NMSC) are now the most common types of cancer in the white populations and the incidence of skin cancer has reached epidemic proportions.
Abstract: Melanoma and non-melanoma (basal and squamous cell carcinoma) skin cancer (NMSC) are now the most common types of cancer in the white populations and the incidence of skin cancer has reached epidemic proportions According to recent population-based studies from Australia the incidence rate is over 2% for basal cell carcinoma in males and 1% for squamous cell carcinoma, and there are over 50 new cases of melanoma per 100 000
TL;DR: Possibility for improvement using the current paradigms of anticoagulation seem limited and new treatment strategies should be developed, as cancer patients with venous thrombosis are more likely to develop recurrent thromboembolic complications and major bleeding during anticoaggerant treatment than those without malignancy.
TL;DR: Interconnecting signaling pathways controlled by RB and p53 are discussed, attempting to explain their potentially universal involvement in the etiology of cancer.
TL;DR: It is concluded that the prevalence of Treg is increased in the peripheral blood as well as in the tumor microenvironment of patients with invasive breast or pancreas cancers, and may partly explain the poor immune response against tumor Ags.
Abstract: Regulatory T cells (T(reg)) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. In mice, depletion of T(reg) by Ab therapy leads to more efficient tumor rejection. T(reg)-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. In this study, we measured the prevalence of T(reg) that coexpress CD4 and CD25 in the PBLs, tumor-infiltrating lymphocytes, and regional lymph node lymphocytes from 65 patients with either pancreas or breast cancer. In breast cancer patients (n = 35), pancreas cancer patients (n = 30), and normal donors (n = 35), the prevalence of T(reg) were 16.6% (SE 1.22), 13.2% (SE 1.13), and 8.6% (SE 0.71) of the total CD4(+) cells, respectively. The prevalence of T(reg) were significantly higher in breast cancer patients (p < 0.01) and pancreas cancer patients (p < 0.01) when compared with normal donors. In tumor-infiltrating lymphocytes and lymph node lymphocytes, the T(reg) prevalence were 20.2% (SE 3.93) and 20.1% (SE 4.3), respectively. T(reg) constitutively coexpressed CTLA-4 and CD45RO markers, and secreted TGF-beta and IL-10 but did not secrete IFN-gamma. When cocultured with activated CD8(+) cells or CD4(+)25(-) cells, T(reg) potently suppressed their proliferation and secretion of IFN-gamma. We conclude that the prevalence of T(reg) is increased in the peripheral blood as well as in the tumor microenvironment of patients with invasive breast or pancreas cancers. These T(reg) may mitigate the immune response against cancer, and may partly explain the poor immune response against tumor Ags.
TL;DR: Generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention are considered and strategies to overcome the various logistic and scientific barriers that impede clinical trials ofNSAIDs for cancer prevention are identified.
Abstract: Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors, have promise as anticancer agents. NSAIDs restore normal apoptosis in human adenomatous colorectal polyps and in various cancer cell lines that have lost adenomatous polyposis coli gene function. NSAIDs also inhibit angiogenesis in cell culture and rodent models of angiogenesis. Many epidemiologic studies have found that long-term use of NSAIDs is associated with a lower risk of colorectal cancer, adenomatous polyps, and, to some extent, other cancers. Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis (FAP). However, unresolved questions about the safety, efficacy, optimal treatment regimen, and mechanism of action of NSAIDs currently limit their clinical application to the prevention of polyposis in FAP patients. Moreover, the development of safe and effective drugs for chemoprevention is complicated by the potential of even rare, serious toxicity to offset the benefit of treatment, particularly when the drug is administered to healthy people who have low annual risk of developing the disease for which treatment is intended. This review considers generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention. We critically examine the published experimental, clinical, and epidemiologic literature on NSAIDs and cancer, especially that regarding colorectal cancer, and identify strategies to overcome the various logistic and scientific barriers that impede clinical trials of NSAIDs for cancer prevention. Finally, we suggest research opportunities that may help to accelerate the future clinical application of NSAIDs for cancer prevention or treatment.
01 Jan 2002
TL;DR: Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin, producing an overall 85% disease-free status.
Abstract: (Reprinted with permission from Ann Intern Med, 87: 293–298, 1997) Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became diseasefree after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 to 30 months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer. Although testicular cancer accounts for only 1% of all malignant tumors in men, it ranks first in incidence of cancer deaths in the 25 to 34 age group. 1 Thus cancer of the testis has a significant impact on the social, economic, and emo
TL;DR: The longer women breast feed the more they are protected against breast cancer, and the lack of or short lifetime duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries.
Journal Article•
TL;DR: It is concluded that large, well-designed studies of common polymorphisms in DNA repair genes are needed and such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.
Abstract: Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.
TL;DR: Cancer incidence and mortality estimates for 1995 are presented for the 38 countries in the four United Nations-defined areas of Europe, using World Health Organization mortality data and published estimates of incidence from national cancer registries to demonstrate the very substantial burden of cancer in Europe, and the scope for prevention.
TL;DR: The clinical features of oral cancer and premalignant oral lesions are reviewed, with an emphasis on early detection.
Abstract: In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in women. The American Cancer Society estimates that 28,900 new cases of oral cancer will be diagnosed in 2002, and nearly 7,400 people will die from this disease. Over 90 percent of these tumors are squamous cell carcinomas, which arise from the oral mucosal lining. In spite of the ready accessibility of the oral cavity to direct examination, these malignancies still are often not detected until a late stage, and the survival rate for oral cancer has remained essentially unchanged over the past three decades. The purpose of this article is to review the clinical features of oral cancer and premalignant oral lesions, with an emphasis on early detection.
TL;DR: Sporting risk-reducing salpingo-oophorectomy in carriers of BRCA mutations can decrease the risk of breast cancer and BRCa-related gynecologic cancer.
Abstract: Background Risk-reducing salpingo-oophorectomy is often considered by carriers of BRCA mutations who have completed childbearing. However, there are limited data supporting the efficacy of this approach. We prospectively compared the effect of risk-reducing salpingo-oophorectomy with that of surveillance for ovarian cancer on the incidence of subsequent breast cancer and BRCA-related gynecologic cancers in women with BRCA mutations. Methods All women with BRCA1 or BRCA2 mutations identified during a six-year period were offered enrollment in a prospective follow-up study. A total of 170 women 35 years of age or older who had not undergone bilateral oophorectomy chose to undergo either surveillance for ovarian cancer or risk-reducing salpingo-oophorectomy. Follow-up involved an annual questionnaire, telephone contact, and reviews of medical records. The time to cancer in the two groups was compared by Kaplan–Meier analysis and a Cox proportional-hazards model. Results During a mean follow-up of 24.2 months...
TL;DR: In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men.
Abstract: Background: Germline BRCA1 mutations confer a substantial lifetime risk of breast and ovarian cancer, but whether cancer at other sites is increased is less clear To evaluate the risks of other cancers in BRCA1 mutation carriers, we conducted a cohort study of 11 847 individuals from 699 families segregating a BRCA1 mutation that were ascertained in 30 centers across Europe and North America Methods: The observed cancer incidence was compared with the expected cancer incidence based on population cancer rates Relative risks (RRs) of each cancer type in BRCA1 carriers relative to risks for the general population were estimated by weighting individuals according to their estimated probability of being a mutation carrier All statistical tests were two-sided Results: BRCA1 mutation carriers were at a statistically significantly increased risk for several cancers, including pancreatic cancer (RR = 226, 95% confidence interval [CI] = 126 to 406, P = 004) and cancer of the uterine body and cervix (uterine body RR = 265, 95% CI = 169 to 416, P<001; cervix RR = 372, 95% CI = 226 to 610, P<001) There was some evidence of an elevated risk of prostate cancer in mutation carriers younger than 65 years old (RR = 182, 95% CI = 101 to 329, P = 05) but not in those 65 years old or older (RR = 084, 95% CI = 053 to 133, P = 45) Overall, increases in the risk for cancer at sites other than the breast or ovary were small and evident in women (RR = 230, 95% CI = 193 to 275, P = 001) but not in men (RR = 095, 95% CI = 081 to 112, P = 58) Conclusions: In carriers of BRCA1 mutations, the overall increased risk of cancer at sites other than breast and ovary is small and is observed in women but generally not in men BRCA1 mutations may confer increased risks of other abdominal cancers in women and increased risks of pancreatic cancer in men and women
TL;DR: This year's report contained a special feature focusing on implications of age and aging on the U.S. cancer burden.
Abstract: BACKGROUND
The American Cancer Society, the National Cancer Institute, the North American Association of Central Cancer Registries (NAACCR), the National Institute on Aging (NIA), and the Centers for Disease Control and Prevention, including the National Center for Health Statistics (NCHS) and the National Center for Chronic Disease Prevention and Health Promotion, collaborated to provide an annual update on cancer occurrence and trends in the United States. This year's report contained a special feature focusing on implications of age and aging on the U.S. cancer burden.
METHODS
For 1995 through 1999, age-specific rates and age-adjusted rates were calculated for the major cancers using incidence data from the Surveillance, Epidemiology, and End Results Program, the National Program of Cancer Registries, and the NAACCR, and mortality data from NCHS. Joinpoint analysis, a model of joined line segments, was used to examine 1973–1999 trends in incidence and death rates by age for the four most common cancers. Deaths were classified using the eighth, ninth, and tenth revisions of the International Classification of Diseases. Age-adjusted incidence and death rates were standardized to the year 2000 population, which places more emphasis on older persons, in whom cancer rates are higher.
RESULTS
Across all ages, overall cancer death rates decreased in men and women from 1993 through 1999, while cancer incidence rates stabilized from 1995 through 1999. Age-specific trends varied by site, sex, and race. For example, breast cancer incidence rates increased in women aged 50-64 years, whereas breast cancer death rates decreased in each age group. However, a major determinant of the future cancer burden is the demographic phenomenon of the aging and increasing size of the U.S. population. The total number of cancer cases can be expected to double by 2050 if current incidence rates remain stable.
CONCLUSIONS
Despite the continuing decrease in cancer death rates and stabilization of cancer incidence rates, the overall growth and aging of the U.S. population can be expected to increase the burden of cancer in our nation. Cancer 2002;94:2766–92. © 2002 American Cancer Society.
DOI 10.1002/cncr.10593
TL;DR: Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelium.
TL;DR: Long-term, disease-free breast cancer survivors reported high levels of functioning and QOL many years after primary treatment, however, past systemic adjuvant treatment was associated with poorer functioning on several dimensions of QOL.
Abstract: Background: Women with breast cancer are the largest group of female survivors of cancer. There is limited information about the long-term quality of life (QOL) in diseasefree breast cancer survivors. Methods: Letters of invitation were mailed to 1336 breast cancer survivors who had participated in an earlier survey and now were between 5 and 10 years after their initial diagnosis. The 914 respondents interested in participating were then sent a survey booklet that assessed a broad range of QOL and survivorship concerns. All P values were two-sided. Results: A total of 817 women completed the follow-up survey (61% response rate), and the 763 disease-free survivors in that group, who had been diagnosed an average of 6.3 years earlier, are the focus of this article. Physical well-being and emotional well-being were excellent; the minimal changes between the baseline and follow-up assessments reflected expected age-related changes. Energy level and social functioning were unchanged. Hot flashes, night sweats, vaginal discharge, and breast sensitivity were less frequent. Symptoms of vaginal dryness and urinary incontinence were increased. Sexual activity with a partner declined statistically significantly between the two assessments (from 65% to 55%, P = .001). Survivors with no past systemic adjuvant therapy had a better QOL than those who had received systemic adjuvant therapy (chemotherapy, tamoxifen, or both together) (physical functioning, P = .003; physical role function, P = .02; bodily pain, P = .01; social functioning, P = .02; and general health, P = .03). In a multivariate analysis, past chemotherapy was a statistically significant predictor of a poorer current QOL (P = .003). Conclusions: Long-term, disease-free breast cancer survivors reported high levels of functioning and QOL many years after primary treatment. However, past systemic adjuvant treatment was associated with poorer functioning on several dimensions of QOL. This information may be useful to patients and physicians who are engaging in discussion of the risks and benefits of systemic adjuvant therapy. [J Natl Cancer Inst 2002;94:39–49]
Erasmus University Rotterdam1, University of Cambridge2, German Cancer Research Center3, Princess Anne Hospital4, University of Manchester5, St George's, University of London6, University of Toronto7, Institute of Cancer Research8, University of London9, University of Pennsylvania10, International Agency for Research on Cancer11, Leiden University12, Wellcome Trust13
TL;DR: The biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCa2 mutations, which is consistent with participation of the encoded proteins in the same pathway.
Abstract: Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (refs 3,4,5). We show that CHEK2(*)1100delC, a truncating variant that abrogates the kinase activity, has a frequency of 1.1% in healthy individuals. However, this variant is present in 5.1% of individuals with breast cancer from 718 families that do not carry mutations in BRCA1 or BRCA2 (P = 0.00000003), including 13.5% of individuals from families with male breast cancer (P = 0.00015). We estimate that the CHEK2(*)1100delC variant results in an approximately twofold increase of breast cancer risk in women and a tenfold increase of risk in men. By contrast, the variant confers no increased cancer risk in carriers of BRCA1 or BRCA2 mutations. This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.
TL;DR: It is shown that primary murine lymphomas also respond to chemotherapy by engaging a senescence program controlled by p53 and p16(INK4a), and mice bearing tumors capable of drug-induced senescENCE have a much better prognosis following chemotherapy than those harboring tumors with senescences defects.
TL;DR: By rationalizing the shared and unique elements of human and mouse models of cancer, this work should be able to identify the molecular circuits that function differently in humans and mice, and use this knowledge to improve existing models ofcancer.
Abstract: Cancer arises from a stepwise accumulation of genetic changes that liberates neoplastic cells from the homeostatic mechanisms that govern normal cell proliferation. In humans, at least four to six mutations are required to reach this state, but fewer seem to be required in mice. By rationalizing the shared and unique elements of human and mouse models of cancer, we should be able to identify the molecular circuits that function differently in humans and mice, and use this knowledge to improve existing models of cancer.