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PubMedDate not supplied

A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer.

PURPOSE: Bladder cancer is still the most common solid tumor among adult males in Egypt because of the prevalence of bilharzial infestation, especially in the countryside. In this prospective study, we have recorded the prognostic factors for 180 patients with invasive bladder cancer for whom standard radical cystectomy had been performed to develop a prognostic index (bladder prognostic index) that defines high risk patients who are more vulnerable to disease relapse after surgery and who may benefit from additional therapy. PATIENTS AND METHODS: The study was performed between January 1997 and December 1999, in which 180 patients with histopathologically proved invasive bladder cancer associated with bilharziasis underwent radical cystectomy or anterior pelvic exenteration. After surgery, patients were regularly followed for a minimum of 2 years. RESULTS: Our patients included 141 males and 39 females. Squamous cell carcinoma was the most common type (53.3%), and most of the tumors were grade II (61.1%). A total of 173 patients had their tumors operable, while 7 were inoperable. We had 5 (2.8%) operative related mortalities. At 5 years postoperatively, free and overall survival rates for the whole group of patients were 31.44%+/-5.9% and 32.5%+/-6.8%, respectively. Tumor pathologic stage, grade, and nodal affection were the only significant factors with impact on survival (P=0.008, 0.051, and 0.004, respectively). These 3 prognostic indexes were used to design a model to predict an individual patient's risk factor for recurrence. Patients were then assigned to one of the 4 risk groups according to the score achieved in this prognostic index (0=low risk, 1=intermediate risk, and 2 or 3=higher risk). These 4 risk groups had distinctly different rates of disease-free survival, i.e., 91.7%, 53%, 13%, and 7% for low, intermediate, and higher risk groups, respectively. CONCLUSION: Although this prognostic index appears to be of a significant clinical relevance, it needs to be more validated on a larger number of patients, and it could be a surrogate variable for biologic factors responsible for the heterogeneity of bladder cancer.

Adult↗
PubMed2005

Fear of recurrence, sense of coherence and posttraumatic stress disorder in haematological cancer survivors.

The diagnosis and treatment of cancer has been shown to precipitate posttraumatic stress disorder (PTSD) in some cancer survivors. However few studies have considered the links between cancer-related PTSD and theoretical models of PTSD. This study considers a cognitive model of PTSD by examining the relationship between sense of coherence, and fear of recurrence to posttraumatic stress symptomatology (PTSS) in haematological cancer survivors. Thirty-six participants completed the PTSD Checklist-Civilian Version (PCL-C), the Impact of Events Scale-Revised (IES-R), the sense of coherence scale and two measures of fear of recurrence. Two measures of fear of recurrence were included as no fear of recurrence measures had previously been assessed for reliability and validity on British populations. Seventeen percent of the sample met DSM-IV diagnostic criteria for PTSD. Statistically significant relationships were found between sense of coherence and fear of recurrence and PTSS, raising questions about the possibility of using this construct as a screening measure for vulnerability to PTSD. A relationship was also found between fear of recurrence and PTSS suggesting that cancer-related PTSS may fit within the theoretical model of PTSD considered. Further examination of factors affecting the onset, maintenance and treatment of PTSD in this population is required.

Adult↗
PubMed1992

Bayesian subset analysis in a colorectal cancer clinical trial.

Subset analysis is the examination of treatment comparisons within groups of patients with restricted levels of patient characteristics. Such analyses are vulnerable to multiplicity effects. We examine the problem in the context of a proportional hazards model with terms for treatment, each of several dichotomous covariates representing the patient characteristics of interest, and treatment-by-covariate interaction effects. Parametrically, a subset-specific treatment effect is equal to the treatment effect term plus a linear combination of the interaction terms. We present Bayesian point and interval estimates under the assumption that the interaction terms are exchangeable and the prior distributions for the other regression parameters are locally uniform. This produces a shrinking of the estimated interaction effects towards zero, thereby discounting them and dealing in a natural way with multiplicity. We illustrate the method using results of a recent North Central Cancer Treatment Group/Mayo Clinic study in advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2026

A targetable dependency on nonsense-mediated decay for cellular homeostasis and immune control in small cell lung cancer.

Small cell lung cancer (SCLC) is one of the most aggressive malignancies, characterized by rapid metastatic dissemination and poor overall survival. Despite harboring excessive alterations, expectedly resulting in immunogenic neoantigens, patients with SCLC remain largely refractory to immunotherapy. We found abundant frameshift mutations in SCLC, regarded as highly immunogenic, counterbalanced by a hyperactive nonsense-mediated decay (NMD) pathway, responsible for frameshift-mRNA degradation. NMD activity correlated with tumor mutational burden (TMB) across cancers, suggesting that SCLC and other TMBhigh cancers may depend on NMD to limit the accumulation of mutation-derived byproducts in order to maintain cellular homeostasis and evade immune recognition. In TMBhigh SCLC models, inhibition of NMD impaired cell proliferation and induced ER stress-dependent apoptosis due to the accumulation of misfolded proteins. Genetic and pharmacological NMD inhibition in vivo effectively controlled TMBhigh tumor growth without overt toxicity. By integrating genome and transcriptome sequencing with MHC-I immunopeptidomics and functional in vitro and in vivo assays, we identified that NMD inhibition boosted neoantigen expression and presentation by tumor cells and increased T cell recognition, thus enhancing overall tumor immunogenicity and further improving immunotherapy efficacy in vivo. Our work shows that SCLC - as a TMBhigh cancer - relies on NMD for survival and immune escape, uncovering a novel TMB-dependent tractable vulnerability for this devastating disease.

Humans↗
PubMed2005

Video preparation for breast cancer treatment planning: results of a randomized clinical trial.

This paper reports results of a randomized controlled trial of a preparatory videotape to reduce distress and increase preparedness among 79 recently diagnosed breast cancer patients. Patients were randomly assigned to view a 19-min video developed for this study, or to a written pamphlet control condition. The video included physician interviews, doctor-patient interaction, and a description of a typical patient's experience at the clinic. Baseline measures included demographic characteristics, history of mental health treatment, personality, and distress (depression, anxiety, helplessness). Outcome measures included distress, quality of life, patient satisfaction, readiness to ask questions of doctor, and participation in the appointment. Results showed that among minority patients, those in the video condition were more satisfied with the overall clinic appointment. Among unmarried patients, those in the video condition tended to have lower distress. Among patients with a history of mental health treatment, those in the video condition tended to have higher quality of life. Among patients working at least half time, those in the video condition were more prepared to ask questions of their doctors. Results suggest that video preparation of cancer patients can be effective, and may be most likely to benefit patients who are vulnerable or underserved.

Aged↗
PubMed2006

Neuronal cell cycle re-entry mediates Alzheimer disease-type changes.

Evidence showing the ectopic re-expression of cell cycle-related proteins in specific vulnerable neuronal populations in Alzheimer disease led us to formulate the hypothesis that neurodegeneration, like cancer, is a disease of inappropriate cell cycle control. To test this notion, we used adenoviral-mediated expression of c-myc and ras oncogenes to drive postmitotic primary cortical neurons into the cell cycle. Cell cycle re-entry in neurons was associated with increased DNA content, as determined using BrdU and DAPI, and the re-expression of cyclin B1, a marker for the G2/M phase of the cell cycle. Importantly, we also found that cell cycle re-entry in primary neurons leads to tau phosphorylation and conformational changes similar to that seen in Alzheimer disease. This study establishes that the cell cycle can be instigated in normally quiescent neuronal cells and results in a phenotype that shares features of degenerative neurons in Alzheimer disease. As such, our neuronal cell model may be extremely valuable for the development of novel therapeutic strategies.

Alzheimer Disease↗
PubMed2005

Is supplementation with elemental diet feasible in patients undergoing pelvic radiotherapy?

BACKGROUND: Acute gastrointestinal upset occurs in approximately 80% of patients undergoing radiotherapy for pelvic cancers. Underlying changes relate to denudation of the mucosal layer which renders the small intestine vulnerable to additional damage from proteolytic enzymes and bile acids. Severe acute bowel symptoms may predispose to progressive fibrotic and ischaemic changes. Elemental diet given during treatment may reduce acute and chronic bowel symptoms induced by pelvic radiotherapy. METHODS: This study aimed to assess compliance with elemental diet during pelvic radiotherapy. Patients with gynaecological, urological or rectal malignancy undergoing radical or adjuvant pelvic radiotherapy were randomised to one of five groups. Each group was assigned a target quantity of three different elemental sip feeds (Group 1, 20%, Group 2, 50%, Group 3, 75% of calorie requirements taken as E028 extra liquid; Group 4, 50% of calorie requirements taken as E028 extra powder; Group 5, 50% of calorie requirements taken as Emsogen powder). Compliance was assessed using a diary card and weekly assessment. Statistical analyses were conducted on an intention to treat basis. RESULTS: Fifty patients (44 female, six male) mean age 58 yr (95% CI 55-61), were recruited to the study (24 endometrial, 17 cervical, 7 rectal, 1 vulval and 1 bladder carcinoma). Mean weight at baseline was 74.5 kg (95% CI 69-80) and this did not change during treatment. Full compliance was achieved in three patients, all from Group 1. By week 5, only 46% of patients were consuming elemental diet. Post hoc analysis of variance with repeated measures indicated that there were no significant differences in volume of elemental diet consumed between groups (P = 0.937). There was a significant inverse linear relationship between intake of elemental diet and time (P < 0.001). CONCLUSIONS: Different formulations of elemental diet do not influence compliance. Patients are unlikely to be able to consume more than one-third of their calorie requirements in the form of an elemental sip feed. Further investigation is warranted to determine if intervention with this volume of elemental diet is beneficial.

Analysis of Variance↗
PubMed2005

[Anticancer drug-induced nephrotoxicity].

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Anti neoplasic drugs have a narrow therapeutic index and the amount of drug necessary to produce a significant reduction in tumour burden usually produces significant nephrotoxicity. The dosage used in clinical trials represents often the maximum tolerated doses determined during phase I drug evaluation. Greater toxicity is acceptable during curative therapy than during palliative therapy. But cancer patients often exhibit excretory reduced organ function. Modulation of pharmacokinetics and pharmacodynamics of these drugs in cancer patients is therefore necessary in order to improve tolerance. Patients with malignancies are particularly vulnerable to development of renal abnormalities. Conversely, patients with renal abnormalities who have undergone kidney transplantation are at high risk for malignancy. Clinical syndromes of renal involvement are diverse and sometimes insidious. Despite the recent advances in understanding the mechanism of anticancer drug nephrotoxicity, prevention still relies on drug dosage decrease and active screening for renal abnormalities as part of the usual biological work up in patients treated with anticancer drugs.

Antineoplastic Agents↗
PubMed1984

Coping with cancer among holocaust survivors in Israel: an exploratory study.

The psychosocial coping potential of Israeli cancer patients who are concentration camp survivors was found to be consistently lower than that of similar cancer patients without camp experience. "The survivor's syndrome" is referred to as explaining the lower coping levels of patients for whom cancer diagnosis reactivates past traumas. The need for early identification and treatment of these highly vulnerable patients is emphasized.

Anger↗
PubMed1997

Modulation of chemosensitivity through altered expression of cell cycle regulatory genes in cancer.

Alterations in the expression of genes affecting cell cycle progression occur in all human cancers. These may occur either by overexpression of genes such as cyclin D1, mutation of regulatory genes such as p16, or abrogation of checkpoints following DNA damage as in the cases of mutation or deletion of the p53 gene. Perturbation of the normal functions of these genes has a profound effect on cellular proliferation, differentiation and apoptosis. There is increasing evidence that such alterations may modulate the cellular response to treatment with chemotherapeutic agents. In many cases genetic alterations may induce resistance to drug treatment as in the case of mutations of the p53 gene. However, the deregulated expression of cell cycle genes may also increase sensitivity to treatment by directly altering the expression of the target for chemotherapeutic drugs as in the case of deletion of the retinoblastoma gene. It is crucial to understand the interactions between drug mechanisms of action and the genetic alterations in cancer to exploit potential areas in which the alterations found in tumors may constitute potential vulnerability.

Cell Cycle Proteins↗
PubMed2006

Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells.

The phosphatidylinositol 3-kinase/Akt pathway plays a critical role in oncogenesis, and dysregulation of this pathway through loss of PTEN suppression is a particularly common phenomenon in aggressive prostate cancers. The mammalian target of rapamycin (mTOR) is a downstream signaling kinase in this pathway, exerting prosurvival influence on cells through the activation of factors involved in protein synthesis. The mTOR inhibitor rapamycin and its derivatives are cytotoxic to a number of cell lines. Recently, mTOR inhibition has also been shown to radiosensitize endothelial and breast cancer cells in vitro. Because radiation is an important modality in the treatment of prostate cancer, we tested the ability of the mTOR inhibitor RAD001 (everolimus) to enhance the cytotoxic effects of radiation on two prostate cancer cell lines, PC-3 and DU145. We found that both cell lines became more vulnerable to irradiation after treatment with RAD001, with the PTEN-deficient PC-3 cell line showing the greater sensitivity. This increased susceptibility to radiation is associated with induction of autophagy. Furthermore, we show that blocking apoptosis with caspase inhibition and Bax/Bak small interfering RNA in these cell lines enhances radiation-induced mortality and induces autophagy. Together, these data highlight the emerging importance of mTOR as a molecular target for therapeutic intervention, and lend support to the idea that nonapoptotic modes of cell death may play a crucial role in improving tumor cell kill.

Animals↗
PubMed2006

Assessing sexual function in obese women preparing for bariatric surgery.

BACKGROUND: Obesity has become a modern epidemic, increasingly affecting the general population worldwide. Obese people are vulnerable to a variety of co-morbidities, including cardiovascular and pulmonary disease, osteoarthritis, diabetes, cancer and psychiatric conditions, that not only diminish life expectancy but also impair quality of life. Research has shown that obesity is further linked to sexual dysfunction, although relevant studies are limited and further investigation is needed. METHODS: We assessed the sexual function of 60 obese women scheduled to undergo bariatric surgery and 50 healthy controls matched by age, education and marital status. All participants were administered the Female Sexual Function Index (FSFI). Additionally, participants completed the Hospital Anxiety and Depression Scale (HADS). RESULTS: Obese women reported significant impairment on most domains of sexual function, including sexual desire, arousal, lubrication, orgasm, and satisfaction, compared to healthy controls. The observed sexual impairment was associated with BMI but was not entirely attributed to the presence of anxiety or depression. CONCLUSION: Obese women complain of significant sexual impairment. Obesity-related sexual dysfunction appears to be a complex condition linked to a range of social, psychological and biological factors. Clinicians are encouraged to evaluate routinely sexual function in this patient population in order to detect those who are in need of intervention.

Adult↗
PubMed1999

Acute decreases in cerebrospinal fluid glutathione levels after intracerebroventricular morphine for cancer pain.

UNLABELLED: Intracerebroventricular (ICV) morphine administration is effective for the management of refractory cancer pain. Recent preclinical observations of acute depletion of the major endogenous intracellular antioxidant glutathione (GSH) in brain and peripheral organs after ICV morphine in rodents led us to apply microchemical methods to profile the neurochemical effects of ICV morphine in three patients treated for intractable cancer pain. Assessment of morphine, morphine-6-glucuronide, and a panel of endogenous compounds and metabolites in ventricular and cisternal cerebrospinal fluid (CSF) demonstrated transient, postdose increases in morphine and morphine-6-glucuronide in ventricular and cistemal CSF, accompanied by acute decreases in CSF GSH levels. Significant changes were also observed in the CSF levels of 4-hydroxybenzoic acid, homovanillic acid, 5-hydroxyphenyllactic acid, and uric acid. These pilot clinical observations of acute central GSH depletion after ICV morphine suggest a novel mechanism for neuropsychiatric toxicity or preclinical findings, such as hyperalgesia or increased motoric activity observed in nonhuman species after central morphine administration. Because ICV morphine is a mainstay of treatment for refractory cancer pain, elucidation of a mechanism's (or mechanisms') mediating a potential pro-oxidant state in the central nervous system induced by ICV morphine is important. IMPLICATIONS: We observed acute decreases in glutathione levels in cerebrospinal fluid sampled from patients after intracerebroventricular doses of morphine for intractable cancer pain. Such doses may, by depleting the antioxidant glutathione, render the central nervous system vulnerable to damage from oxidative stress.

Chromatography, High Pressure Liquid↗
PubMed1984

Oral candidiasis.

Candidiasis is, by far, the most common mycotic infection of the human oral cavity. The usually manifested clinical expression of oral candidiasis at all ages from the newborn to the elderly is thrush. Other forms that affect the mouth include acute atrophic candidiasis associated with oral antibiotic therapy, chronic atrophic candidiasis attributable to the wearing of full upper dentures, candidal cheilosis ascribable to perlèche or decreased vertical dimension in the lower third of the face, chronic mucocutaneous candidiasis emanating from a T-lymphocyte deficiency, and candidal leukoplakia. Extensive use of antibiotics and immunosuppressive drugs have greatly increased the number of Candida-induced oral infections. Patients debilitated by irradiation, cancer chemotherapy, organ transplants, diabetes mellitus, and defects in cell-mediated immunity are particularly vulnerable. Fortunately, the vast majority of cases of oral candidiasis are not life-threatening and readily respond to appropriately administered anticandida agents. It must always be remembered, however, that the organism has the capacity to produce fulminating fatal infection by hematogenous dissemination from seemingly innocuous oral infections that serve as a portal of entry to the systemic circulation. Consequently, all oral candidal infections in compromised patients must be treated vigorously and effectively.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Epidemiology of cancer and aging.

The incidence of cancer increases with age. Given the increasing older population, one may expect that by the year 2030 about 70% of all malignancies will occur in individuals aged 65 and older. The following information is obtained from clinical epidemiology: the elderly are more vulnerable than are younger individuals to environmental carcinogens and may represent a natural monitoring system for new carcinogens in the environment; the biology of cancer may change with age, with some cancers becoming more aggressive (leukemias, lymphomas, ovarian) and others more indolent (breast, lung); most cancers present at a more advanced stage in the elderly, which suggests underutilization of screening and ignorance of symptoms; cancer affects preferentially healthy older individuals; and multiple cancers become more common with age. On the basis of these findings, preventative and therapeutic strategies for the elderly may be formulated.

Aged↗
PubMed1997

Lucké renal adenocarcinoma, an anuran neoplasm: studies at the interface of pathology, virology, and differentiation competence.

The northern leopard frog, Rana pipiens, is vulnerable to a herpesvirus-induced renal tumor. The Lucké renal adenocarcinoma is metastatic as a function of temperature. The cloning procedure of nuclear transplantation has been used to study the differentiation potential of the tumor genome. This paper summarizes current studies of the pathology, virology, and differentiation competence of the Lucké tumor.

Adenocarcinoma↗
PubMedDate not supplied

Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients.

OBJECTIVE: Prior research suggests that the diagnosis and treatment of cancer can result in the development of symptoms of posttraumatic stress disorder (PTSD). Based on Lazarus and Folkman's model of stress, the current study examined whether trauma appraisals, coping, social support, and social constraint were associated with the severity of PTSD symptoms in cancer patients who had undergone bone marrow transplantation (BMT). METHODS: Participants were 23 males and 79 females treated with BMT an average of 20 months previously (range = 3-62 months). Past and current psychiatric diagnoses were assessed through a structured clinical interview. PTSD symptomatology and other psychological variables were assessed using standardized self-report measures. RESULTS: Results indicated that 5% of participants met diagnostic criteria for current PTSD. Participants reported an average of three to four symptoms of PTSD (range = 0-16). Univariate analyses confirmed predictions that increased PTSD symptomatology would be associated with more negative appraisals of the BMT experience, greater use of avoidance-based coping strategies, lower levels of social support, and greater social constraint (p < .05). Regression analyses indicated that each of these variables accounted for significant (p < .05) variability in PTSD symptomatology above and beyond relevant demographic and medical variables. CONCLUSIONS: Results of the present study confirm and extend prior research regarding the prevalence of PTSD and PTSD symptoms among patients treated for cancer. In addition, the study identified a set of theoretically derived psychological characteristics that seem to place patients at risk for greater PTSD symptomatology after BMT.

Adaptation, Psychological↗
PubMed1998

[Self-assessment of vulnerability to illness by the Austrian population].

Results of a Cross-Sectional Study in 1995: The self-perceived threat of cancer, myocardial infarction, stroke, traffic accidents, diabetes mellitus, AIDS, Alzheimer's Disease and drug abuse was investigated in a survey among a representative sample of Austrians (aged > or = 15 years) in 1995. The most feared disease was cancer (41%), followed by traffic accidents (38%) and myocardial infarction (36%). The disease feared least was drug abuse (6%). Females feared cancer, stroke, diabetes mellitus and Alzheimer's disease significantly more than males. A cluster analysis reveals that respondents who perceive a higher threat by the diseases have low levels of education and live in rural areas. The age distribution of persons who responded with "very threatening" corresponds well with the age-specific prevalence of the disease. Smoking habits, alcohol consumption and body-mass index have no influence on the self-perceived threat of the investigated diseases.

Adolescent↗