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PubMed1990

[Experience in cancer of the uterine cervix treated with surgery--an analysis of 820 cases].

From 1962 to November 1985, 1000 cases of cervical cancer were treated surgically, of whom 820 (37 Stage 0, 371 Stage I, 399 Stage II, 10 Stage III and 3 Stage IV lesions) had been operated before 1982. In the 820 cases, squamous cell cancer comprised 90.5%, adenocarcinoma 8.8% and adenoacanthoma or adenosquamous cancer 0.7%. Pelvic lymph node metastasis rate was 8.9% and 24.1% in Stages I and II. The obturator region was the most vulnerable to metastasis. The 5-year survival rate was 86.7% in 173 cases of infiltrative cancer treated during 1978-1982. The 10-year survival rate was 85.25% (520/610) in the infiltrative cancer, 95.9% in Stage I and 75.3% in Stage II. Two cases with Stage IV without pelvic lymph node metastasis treated with surgery have survived for over 10 years. All thirty-seven cases of cervical cancer in situ treated with surgery are still alive. Pelvic lymph node metastasis is the major factor influencing operation and survival.

Adenocarcinoma↗
PubMed2004

The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers.

Signaling through the B cell antigen receptor promotes activation and survival of mature B cells. B cell-activating factor belonging to the tumor necrosis factor family (BAFF) is another critical survival factor for B cells, and is also necessary for B cell maturation. Abnormal production of BAFF disturbs immune tolerance by allowing the survival of autoreactive B cells, thus triggering autoimmune disorders. BAFF can also have an important impact on B cell malignancies. In contrast to normal B cells, malignant B cells show uncontrolled cell proliferation. BAFF levels are elevated in the serum of patients with systemic autoimmune diseases, and, importantly, in patients with B-lymphoid malignancies. Furthermore, BAFF is produced by malignant B cells and acts as an essential autocrine survival factor. The strong dependence of certain lymphoid cancer cells on BAFF might be a point of vulnerability, which offers exciting new therapeutic possibilities.

Antibodies, Monoclonal↗
PubMedDate not supplied

T cell differentiation and cytokine expression in late life.

Elderly humans are at significant risk with regard to the incidence and severity of many infectious diseases and cancers. Current theory holds that these late-life vulnerabilities arise, in part, through age-related changes in immune function, particularly in the T lymphocyte lineage. Herein, we discuss how such factors as thymic involution and ongoing T cell differentiation in the peripheral tissues contribute to progressive and irreversible shifts in the state of differentiation of the mature T cell pool. We propose that, by late life, these processes yield a T cell compartment with a suboptimal balance of naive and memory T cell subsets, each with altered, subset-specific programs for cytokine gene expression. As such, the T cell compartment in late life may be more prone to immune deficiency or cytokine-mediated dysregulation in response to new or previously encountered pathogens.

Age Factors↗
PubMed2003

Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism.

Cancer cells are under intrinsic increased oxidative stress and vulnerable to free radical-induced apoptosis. Here, we report a strategy to hinder mitochondrial electron transport and increase superoxide O2. radical generation in human leukemia cells as a novel mechanism to enhance apoptosis induced by anticancer agents. This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I. Partial inhibition of mitochondrial respiration enhances electron leakage from the transport chain, leading to an increase in O2. generation and sensitization of the leukemia cells to anticancer agents whose action involve free radical generation. Using leukemia cells with genetic alterations in mitochondrial DNA and biochemical approaches, we further demonstrated that As2O3, a clinically active anti-leukemia agent, inhibits mitochondrial respiratory function, increases free radical generation, and enhances the activity of another O2.-generating agent against cultured leukemia cells and primary leukemia cells isolated from patients. Our study shows that interfering mitochondrial respiration is a novel mechanism by which As2O3 increases generation of free radicals. This novel mechanism of action provides a biochemical basis for developing new drug combination strategies using As2O3 to enhance the activity of anticancer agents by promoting generation of free radicals.

2-Methoxyestradiol↗
PubMed2006

Relation between concentration of air pollution and cause-specific mortality: four-year exposures to nitrogen dioxide and particulate matter pollutants in 470 neighborhoods in Oslo, Norway.

This study investigated the concentration-response relation between air pollution (nitrogen dioxide and particulate matter pollutants PM(10) and PM(2.5)) and cause-specific mortality. The population included all inhabitants of Oslo, Norway, aged 51-90 years on January 1, 1992 (n = 143,842) with follow-up of deaths from 1992 to 1998. An air dispersion model (AirQUIS; Norwegian Institute for Air Research (NILU), Oslo, Norway) was used to estimate levels of exposure in 1992-1995 in all 470 administrative neighborhoods. These data were linked to census, education, and death registries. A consistent effect on all causes of death was found for both sexes and age groups by all indicators of air pollution. The effects appeared to increase at nitrogen dioxide levels higher than 40 micro g/m(3) in the youngest age group and with a linear effect in the interval 20-60 micro g/m(3) for the oldest. An effect of all indicators on cardiovascular causes, lung cancer, and chronic obstructive pulmonary disease was also found in both age groups and sexes. The effects were particularly strong for chronic obstructive pulmonary disease, which appeared to have linear effects, whereas cardiovascular causes and lung cancer seemed to have threshold effects. Results show that vulnerable persons with chronic obstructive pulmonary disease and the elderly seem to be susceptible to air pollution at lower levels than the general population.

Aged↗
PubMedDate not supplied

Effects of 17beta-estradiol and progesterone on transcription of human papillomavirus 16 E6/E7 oncogenes in CaSki and SiHa cell lines.

Several in vitro studies have addressed the interactions between estrogen/progesterone and human papillomavirus (HPV), but the results are controversial. We evaluated the effects of estrogen and progesterone and their antagonists on messenger RNA expression of HPV16 E6/E7 in HPV16-positive cell lines CaSki and SiHa with real-time reverse-transciptase polymerase chain reaction method. Colorimetric assay with tetrazolium salt (WST-1) and flow cytometry were used for testing proliferation and apoptosis. No statistically significant changes were found after hormone treatment in the expression of HPV16 E6/E7 or hormone receptors in CaSki and SiHa cell lines. Progesterone increased cell proliferation in both the cells, while estrogen increased proliferation of SiHa cells only. Estrogen seemed to protect the CaSki cells from apoptosis, and tamoxifen did not abrogate this effect. Progesterone slightly increased apoptosis of CaSki cells, and this effect was neutralized with RU486. In this study, estrogen and progesterone did not change either the transcription levels of HPV16 E6/E7 or estrogen receptor or progesterone receptor levels. Hormone receptor antagonists had no effect on transcription. Both hormones might have a permissive effect for the growth of cervical cancer, by promoting cell proliferation and making the cells vulnerable to mutations. In addition, estrogen acts as an antiapoptotic agent allowing growth advance of the cells infected with oncogenic HPV.

Apoptosis↗
PubMed2004

Factors predicting prostate specific antigen testing among first-degree relatives of prostate cancer patients.

First-degree relatives (FDRs) of prostate cancer patients are known to be at increased risk for the disease, yet relatively little is known about their screening behaviors. The current lack of consensus about the value of prostate cancer screening underscores the importance of examining why some men at increased risk participate in screening and others do not. In this study, variables from Protection Motivation Theory were used to identify predictors of prostate specific antigen (PSA) testing in this at-risk population. Toward this end, scales assessing perceived vulnerability, perceived severity, response efficacy, and self-efficacy for prostate cancer screening were administered to 82 unaffected male FDRs aged 40 and older. When recontacted approximately 14 months later, 50% of FDRs were found to have undergone PSA testing in the interim. Older age, prior prostate cancer screening, and a greater sense of personal efficacy about being able to undergo prostate cancer screening were found to be significant (P < 0.05) predictors of subsequently undergoing PSA testing. These findings provide partial support for the predictive validity of Protection Motivation Theory variables and suggest the importance of considering efficacy beliefs in attempting to understand decision-making about PSA testing in at-risk individuals.

Age Distribution↗
PubMed2002

The diet, prostate inflammation, and the development of prostate cancer.

Evidence that somatic inactivation of GSTP1, encoding the human pi-class glutathione S-transferase, may initiate prostatic carcinogenesis is reviewed along with epidemiological evidence implicating several environment and lifestyle factors, including the diet and sexually transmitted diseases, as prostate cancer risk factors. An integrated model is presented featuring GSTPI function as a 'caretaker' gene during the pathogenesis of prostate cancer, in which the early loss of GSTPI activity renders prostate cells vulnerable to genome damage associated with chronic prostatic inflammation and repeated exposure to carcinogens. The model predicts that the critical prostate carcinogens will be those that are substrates for GSTP1 detoxification and are associated with high prostate cancer risk diet and lifestyle habits.

Cell Transformation, Neoplastic↗
PubMed2026

Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.

For the past decades, chemotherapy constituted the therapeutic foundation in advanced or metastatic pancreatic cancer. Despite significant advances in the molecular understanding, translation into tangible patient benefit has remained modest. Until recently, mutant KRAS, the dominant oncogenic driver, was considered undruggable, and only a small subgroup of patients potentially benefited from targeted therapies. With the emergence of KRAS inhibitors, most patients with pancreatic cancer in theory qualify for targeted therapeutics. Final results from the RASolute 302 trial showed clinically meaningful activity of RAS inhibition in patients with metastatic pancreatic cancer and paved the way for approval. Ongoing preclinical and coclinical studies have documented both intrinsic and acquired mechanisms of resistance to KRAS inhibition. Given the cellular plasticity seen in pancreatic cancer, the identification and anticipation of resistance mechanisms will be critical to exploit emerging therapeutic vulnerabilities through novel combination strategies. In view of the increasing number of trials and the growing body of evidence for targeted therapies, pancreatic cancer is entering a transitional phase in which precision oncology strategies must be redefined beyond rare molecular subgroups. In this review, we will briefly revisit targeted therapeutic approaches in pancreatic cancer to then discuss the clinical implications of genomic and transcriptomic heterogeneity in KRAS-mutant and KRAS wild-type disease. We will outline how our expanding biological insights into pancreatic cancer could inform combination and sequential therapeutic approaches.

Humans↗
PubMed2004

Challenges in conducting research with hospitalized older people with cancer: drawing from the experience of an ongoing interview-based project.

Older people with cancer often face the prospect of cognitive and physical frailty, increased vulnerability of psychological distress and limited access to resources. These factors present ethical and methodological challenges for conducting research in such patients, especially interviews in acute care settings. This paper discusses these challenges using experiences from an ongoing research project. The project is a patient-focused study on the perceptions of older people with cancer regarding information provided to them, decision making and treatment. Interviews with patients aged 65 or over with a cancer diagnosis are conducted in two clinical settings, care of the elderly wards and a cancer centre whilst they are in-patients. Patients' cognitive and physical status are assessed using clinical measures, whereas socio-demographic and medical data are obtained from patient files. Ethical challenges, including procedures to obtain valid consent, as well as methodological choices, including recruitment procedures and patient conditions are presented and debated with reference to previous literature. Suggestions for future research with older people with cancer are made based both on current experience and previous literature.

Aged↗
PubMedDate not supplied

Estradiol and progesterone can prevent rat mammary cancer when administered concomitantly with carcinogen but do not modify surviving tumor histology, estrogen receptor alpha status or Ha-ras mutation frequency.

An early full-term pregnancy is protective against mammary cancer in both humans and rodents. Treating rats with two hormones of pregnancy, estradiol and progesterone, for 5 weeks renders the rat mammary glands refractory to carcinogenesis. Our objectives was to determine if a shortened regimen (3 weeks) would be as effective as the 5-week regimen and to determine if the mammary gland was vulnerable to carcinogenic insult during the hormone treatments. We also examined cancers that survived the chemopreventive regimen to see if those tumors were particularly aggressive compared to control tumors (i.e., less differentiated, estrogen receptor alpha (ER alpha)-negative or harbored mutations in Ha-ras). In the first experiment, Lewis rats were injected with N-methyl-N-nitrosourea (MNU, 50 mg/kg) at 50 days of age. At 60 days of age, the rats were either mated and allowed to nurse their young for 3 weeks, treated with hormone vehicle for 5 weeks, or 17 beta-estradiol (E, 20 micrograms) and progesterone (P, 4 mg) 5 times per week for 3 or 5 weeks. All the rats exposed to MNU but not estradiol and progesterone developed multiple mammary cancers. Pregnancy reduced multiplicity to 0.40 cancers/rat. Treatments of estradiol and progesterone for 3 or 5 weeks reduced cancer multiplicity and increased latency to a similar degree as pregnancy. Mammary cancers from each group displayed a similar spectra of histologic class, estrogen receptor alpha (ER alpha) content and Ha-ras mutation status. In the second experiment, 50-day-old rats were treated for five weeks with either estradiol and progesterone or vehicle as above beginning at 60 days of age and treated with MNU at 50, 64, 78 or 92 days of age. In each case, estradiol and progesterone treatments resulted in significantly reduced mammary tumor frequency. These results demonstrate that a three-week regimen of estradiol and progesterone can protect the mammary gland from chemically-induced carcinogenesis even when carcinogen exposure occurs concomitant with estradiol and progesterone stimulation.

Animals↗
PubMed2004

Amputee skiers: lofty ambassadors in the rehabilitation of cancer.

Adolescence is characterized by inter-related physiologic and emotional development. It is a particularly vulnerable period of life culminating into emergence as an adult. The majority of malignant bone tumors in pediatrics affect the adolescent patient. As a part of the treatment, amputation may be required for cure. This often creates a "grieving process. " Adjustment to this process is described. At the M. D. Anderson Cancer Center to assist in functional and emotional rehabilitation, an annual ski trip for amputees has been held over the past two decades. The accomplishments of this trip are outlined. Motivated by the success of the program, preadolescent amputees and blind and paraplegic cancer patients were also invited to participate. The adolescent amputee paved the way for rehabilitating other physically challenged cancer patients!

Adolescent↗
PubMed2025

De novo pyrimidine synthesis is a collateral metabolic vulnerability in NF2-deficient mesothelioma.

Pleural mesothelioma (PM) is one of the deadliest cancers, with limited therapeutic options due to its therapeutically intractable genome, which is characterized by the functional inactivation of tumor suppressor genes (TSGs) and high tumor heterogeneity, including diverse metabolic adaptations. However, the molecular mechanisms underlying these metabolic alterations remain poorly understood, particularly how TSG inactivation rewires tumor metabolism to drive tumorigenesis and create metabolic dependencies. Through integrated multi-omics analysis, we identify for the first time that NF2 loss of function defines a distinct PM subtype characterized by enhanced de novo pyrimidine synthesis, which NF2-deficient PM cells are critically dependent on for sustained proliferation in vitro and in vivo. Mechanistically, NF2 loss activates YAP, a downstream proto-oncogenic transcriptional coactivator in the Hippo signalling pathway, which in turn upregulates CAD and DHODH, key enzymes in the de novo pyrimidine biosynthesis pathway. Our findings provide novel insights into metabolic reprogramming in PM, revealing de novo pyrimidine synthesis as a synthetic lethal vulnerability in NF2-deficient tumors. This work highlights a potential therapeutic strategy for targeting NF2-deficient mesothelioma through metabolic intervention.

Pyrimidines↗
PubMed2006

Temperament as a predictor of internalising and externalising problems in adolescent children of parents diagnosed with cancer.

OBJECTIVE: This study examined the relationship between temperament and internalising and externalising problems among children of parents diagnosed with cancer, beyond the effects of socio-demographics, illness-related variables and life events. MATERIALS AND METHODS: Three hundred and forty adolescent children and their 212 parents diagnosed with cancer participated. Children and parents completed the Youth Self Report and the Child Behaviour Checklist, respectively. Children completed also the Early Adolescent Temperament Questionnaire. MAIN RESULTS: Daughters of parents with cancer were reported as having more internalising problems than their counterparts did. Prevalence of problems did not depend on children's and parents' age or educational level. Recurrent disease and number of life events experienced by children and parents affected the problems reported. The most important temperament dimensions in the prediction of internalising problems in children were shyness and fear/worry, to a lesser extent, frustration and perceptual sensitivity (children only) and lower scores on pleasure intensity (parents only). Externalising problems were associated with effortful control and in children's reports with frustration. Temperament seemed to be a more important predictor of problems reported by children than parents. CONCLUSION: Findings suggest that temperament is useful in determining the relative vulnerability of children of parents who have been diagnosed with cancer. Social workers may help parents to recognise individual differences between children and to support children by using techniques that are compatible with the temperament of children.

Adolescent↗
PubMed1997

Psychological distress in women seeking genetic counseling for breast-ovarian cancer risk: the contributions of personality and appraisal.

The purpose of the present study was two-fold: (a) to characterize the psychological status of women with a family history of breast or ovarian cancer who self-refer for genetic counseling and BRCA1 testing; and (b) to identify specific demographic, personality, and appraisal factors that contribute to cancer-specific distress and general distress in this group of women. Participants were 256 women ages 18 and older who had at least one first-degree relative (FDR) with breast and/or ovarian cancer. Participants were recruited through breast cancer clinics and obstetrics/gynecology departments at two medical centers by responding to program information described in a brochure. The results revealed moderate distress levels in this population. The results of a hierarchical regression of general distress indicated that women with higher levels of general distress were less likely to be married, less optimistic, and had heightened breast cancer risk perceptions accompanied by feelings of low perceptions of control over the development of breast cancer (R2 = .44, p = .0001). Women with higher levels of cancer-specific distress tended to be younger and non-White and had low perceptions of control over developing breast cancer (R2 = .15, p = .0002). These findings suggest that self-referred genetic counseling participants may be psychologically vulnerable and may benefit from interventions designed to decrease distress and the perceived absence of control over developing breast cancer.

Adaptation, Psychological↗
PubMed1997

Factors distinguishing regular readers of breast cancer information in magazines.

This study examined the differences between women who were regular and occasional readers of breast cancer information in magazines. Based on uses and gratifications theory and the Health Belief Model, women respondents (n = 366) were predicted to differentially expose themselves to information. A discriminant analysis showed that women who were regular readers reported greater fear, perceived vulnerability, general health concern, personal experience, and surveillance need for breast cancer-related information. The results are discussed in terms of the potential positive and negative consequences of regular exposure to breast cancer information in magazines.

Adult↗
PubMed2004

The talking touchscreen: a new approach to outcomes assessment in low literacy.

PURPOSE: Cancer patients who are deficient in literacy skills are particularly vulnerable to experiencing different outcomes due to disparities in care or barriers to care. Outcomes measurement in low literacy patients may provide new insight into problems previously undetected due to the challenges of completing paper-and-pencil forms. DESCRIPTION OF STUDY: A multimedia program was developed to provide a quality of life assessment platform that would be acceptable to patients with varying literacy skills and computer experience. One item at a time is presented on the computer touchscreen, accompanied by a recorded reading of the question. Various colors, fonts and graphic images are used to enhance visibility, and a small picture icon appears near each text element allowing patients to replay the sound as many times as they wish. Evaluation questions are presented to assess patient burden and preferences. RESULTS: An ethnically diverse group of 126 cancer patients with a range of literacy skills and computer experience reported that the 'talking touchscreen' (TT) was easy to use, and commented on the usefulness of the multimedia approach. CLINICAL IMPLICATIONS: The TT is a practical, user-friendly data acquisition method that provides greater opportunities to measure self-reported outcomes in patients with a range of literacy skills.

Adult↗
PubMed1993

Bronchogenic carcinoma: immunologic aspects.

Evidence that host immunologic function may influence the behavior of lung cancer is accumulating. Non-small-cell lung cancers are heavily infiltrated by host lymphocytes. The fact that monoclonal antibodies have been developed against lung cancer cells implies that such cells express surface antigens and are therefore vulnerable to immune recognition. Failure of the host defense mechanism to control tumor growth may involve (1) reduced natural killer cell activity, (2) inadequate lymphokine-activated killer cell function, or (3) tumor secretion of immunomodulating factors. Basic immunologic research studies of lung cancer are increasing the potential for clinical applications. New monoclonal antibodies have improved both the sensitivity and the specificity of immunohistopathologic analyses of pulmonary specimens. Links between immune function and prognosis in patients with lung cancer have been established. Finally, initial results from protocols that have used tumor-infiltrating lymphocytes, interleukin 2, and tumor vaccines suggest that immunobiologic treatment modalities may be increasingly applicable in patients with lung cancer.

Antibodies, Neoplasm↗