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PubMed1999

Psychosocial adjustment of pediatric patients after allogeneic stem cell transplantation.

The purpose of this study was to assess the psychosocial adjustment of patients who had been treated with allogeneic stem cell transplantation (SCT) in our clinic. Selection criteria for patients were to be aged 14-30 years at the time of the follow-up, to be at least 2 years post-SCT and to have a very good knowledge of German. Among 31 eligible patients, 26 participated (84% response rate). The patients were between 15 and 27 years old and were on average 7 years (range 2-13) post-SCT. Research instruments consisted of a demographic questionnaire and various subscales of established psychological measures for which data from a sample of bone cancer survivors and population norms were available. About 35% of patients showed high levels of anxiety, 62% appeared to be extremely sensitive and vulnerable, and 35% showed strong, unfulfilled needs in their love lives. In the other domains tested (self-esteem, family and peer relationships, school/vocational performance, etc), no noticeable differences were found between the subjects and comparable populations. There was no significant association between psychosocial outcome and demographic features or clinical data. Our results suggest that patients who underwent SCT in their childhood or adolescence are at risk of developing long-term emotional or social problems. Due to the retrospective design of our study and the small sample size, no predictive factors for psychosocial distress could be identified.

Adolescent↗
PubMed2004

Impairments of attention following treatment with cranial irradiation and chemotherapy in children.

Neurobehavioral impairments are frequently reported following treatment for childhood cancers, with cranial irradiation (CRT). This study investigated attention and information processing skills, predicting that these skills would be impaired due to the vulnerability of cerebral white matter in early childhood. Three treatment groups were studied: (i) CRT+chemotherapy (n = 35); (ii) chemotherapy alone (n = 19); (iii) healthy children (n = 35). All children were aged 9 to 16 years at time of assessment, with no pre-diagnosis history of neurologic, developmental, or psychiatric disorder. Children were administered a series of task measuring processing speed and sustained, selective, and shifting attention. For children treated with CRT + chemo, results identified residual deficits in processing speed for complex tasks, selective and shifting attention. In contrast, processing speed was intact for simple tasks, and there was no clear evidence of deterioration in performance over time, as might be expected in the presence of a sustained attention deficit. Children treated with chemotherapy alone demonstrated generally intact attentional skills. However, this group did record an increasing number of attentional lapses over time on tasks tapping sustained attention skills.

Adolescent↗
PubMed2026

Fault Lines in the Genome: Somatic DNA Mutations in Aging and Neurodegeneration.

The human genome is both fragile and resilient: prone to alteration yet protected by extensive repair mechanisms. With age, individuals accumulate genetic damage from environmental factors and cell-intrinsic processes, with effects ranging from benign nucleotide shifts to disease-driving mutations. Such alterations to the genetic code outside the germline are described as somatic mutations and display striking heterogeneity across cell types. Recently, somatic mutations have emerged as a hallmark feature of aging in the body's longest-lived tissue: the central nervous system (CNS). The distinctively long lifespan, high metabolism, electrochemical activity, and unique epigenome of CNS cells may render them especially vulnerable to mutational accumulation. The CNS therefore provides a model for understanding how somatic mutations drive cellular dysfunction beyond an established role in cancer. Here, we review the somatic mutations that arise in the brain across lifespan, the mechanisms that lead to their formation, and their potential contributions to aging and age-related disease.

Journal Article↗
PubMed1996

Counseling needs of women with breast cancer: what the women tell us.

Research has demonstrated that some women treated for breast cancer are at risk for significant and persistent emotional distress and disrupted quality of life. Factors identified that appear to make women psychologically vulnerable include younger age at diagnosis, a history of high life stress or depression prior to diagnosis, and more advanced disease. Research has quickly moved to develop and implement psychological interventions to help these women, although little is known about the patients' perceptions of their need for, and use of, such services. This article presents research that focuses on the perceptions of the women themselves using a survey technique.

Adaptation, Psychological↗
PubMed1999

Massaged embodiment of cancer patients.

This paper analyses the massaged embodiment of cancer patients and involves a poststructural approach. Poststructuralism as a methodology is used as it provides a way of seeing and understanding cancer patients' complex experience of embodiment. Massage promotes a quality of embodiment that involves well being, comfort and relaxation. However, massage can promote vulnerability and this is evident in some of the participants' talk. For participants, massage provides a reclaiming of 'the old body' and an experience of mind and body connection. Embodiment is theorised as shifting, discursively constituted and multi layered.

Body Image↗
PubMed1988

New understanding from epidemiology--the next 25 years.

The epidemiology of radiation carcinogenesis is likely to be dominated during the next 25 y by the gradual maturation of major studies of populations exposed to substantial levels of radiation dose. During this period, for example, most of the new information on cancer risk among survivors of the 1945 atomic bombings of Hiroshima and Nagasaki will pertain to persons exposed at ages under 30. From the A-bomb survivor data and from a number of medically and occupationally irradiated populations now under study, it will be possible to construct a fairly complete picture of the temporal distribution of excess cancer risk over the remaining life span following exposure, a major source of uncertainty and controversy in current risk estimates. Provided that the necessary efforts are made, it should be possible to greatly increase our understanding of which organs and tissues are vulnerable to radiation carcinogenesis, variation by age at exposure and sex, and (what is most difficult at the present time) the influence of other risk factors and possible modifying factors on the magnitude of risk associated with radiation exposure. For some sites it may be possible, as it is now for breast cancer, to rule out certain broad classes of simple dose-response models. While the data gathered during the next 25 y will be nearly the last from some very important series, their information content should be extremely high. Thus, there is every reason to improve the resources, e.g., by improving dosimetry, enlarging samples, tapping new sources of case ascertainment, and gathering information on factors other than radiation dose. Modeling in epidemiological investigations depends heavily on work in experimental radiobiology. Thus far, the exchange has been largely in one direction, since epidemiological study design is mostly a matter of extracting information from "experiments" that have already taken place. With more epidemiological information, it seems reasonable to hope that detailed hypotheses, with direct relevance to areas of epidemiological uncertainty, may be generated suitable for experimental investigation. It seems likely that findings from large studies of populations exposed to relatively low levels of radiation, for which the signal-to-noise ratio is low, and for which random error and subtle sources of bias may have more than usual influence on reported results, will continue to generate controversy.(ABSTRACT TRUNCATED AT 400 WORDS)

Accidents↗
PubMed2000

Breast and cervical cancer screening for older women: recommendations and challenges for the 21st century.

The incidence of both breast and cervical cancer increases with age, and older socioeconomically disadvantaged and minority women are most likely to develop or die of these diseases. Early detection has the potential to decrease the disproportionate burden of disease in these vulnerable groups at a reasonable cost to society. Yet despite impressive overall gains in use of mammography and Pap smears, older women, especially older minority women, remain underrepresented in screening programs. Physician recommendation is one of the most powerful predictors of screening across all age, socioeconomic, and ethnic groups. The overwhelming majority of older women, make one or more physician visits each year, each of which represents an opportunity to screen for breast and cervical cancer. Although older women will accept screening if it is offered by their providers, physicians are less likely to offer it to them than to their younger, white patients. Conflicting professional recommendations for screening older women, leaving older women out of clinical trials of screening efficacy, competing causes of mortality with increasing age, and possible negative attitudes held by physicians and patients all contribute to the underscreening of older women. Cancer control challenges for the next century include defining groups of women most likely to benefit from screening (based on age, disease risk, competing mortality, and quality of life), improving regular use of early detection, educating providers, and conducting research on age-mediated differences in breast or cervical cancer biology that could affect screening recommendations.

Aged↗
PubMedDate not supplied

Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy.

Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the "host versus tumor response," thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy, in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer, immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery, chemotherapy and/or radiotherapy.

Adjuvants, Immunologic↗
PubMed2026

Mechanism-Driven Diagnostic Development: A Specimen-Aware Framework Illustrated by Colorectal Cancer and Solid Tumours.

Translational oncology has moved rapidly from histopathology and single-analyte biomarkers toward multi-dimensional molecular profiling. Yet many clinically deployed tests still use reductionist biomarker strategies that under-represent cancer complexity. This review examines whether a mechanistic, multi-layered, and specimen-aware approach can improve cancer detection, classification, prognosis, minimal residual disease (MRD) assessment, and therapeutic selection. Evidence across solid tumours shows that genomic alterations alone incompletely explain tumour state, metastatic behaviour, immune evasion, or therapeutic vulnerability. Integrated genome and transcriptome analyses, proteogenomics, single-cell atlases, fragmentomic, methylation based cell-free DNA assays, metabolomics and microbiome assessments reveal clinically relevant biology that single modality tests cannot determine. Minimally invasive collected specimens can extend access to screening, diagnosis and longitudinal monitoring, but the choice of specimen should be matched to disease biology and analytes that represent mechanisms of oncogenesis. However, translation remains constrained by pre-analytical variability, contamination, differences in tumour shedding behaviour, clonal haematopoiesis, translation of generated models, incomplete external validation and uncertain downstream clinical utility for emerging platforms. This review provides a commentary on the future of cancer diagnostics, the considerations and barriers to clinical translation, the relationship between utility and dimensionality of biomarkers assessed and the emerging rationale towards mechanistically grounded integrated models.

biomarkers↗
PubMed1998

Psychosocial stress moderates the relationship of cancer history with natural killer cell activity.

Data suggest that both cancer history and psychosocial stress may be associated with reductions in natural killer cell activity (NKA). Therefore, we tested whether individual differences in cancer history, chronic/perceived stress, and their interactions would be associated with decreased levels of NKA. We tested these hypotheses in 80 spouse caregivers of victims of Alzheimer's Disease (AD) (persons known to report high levels of psychosocial stress) and in 85 age- and sex-matched spouses of non-demented controls. Participants were assessed at study entry (Time 1) and 15-18 months later (Time 2). Individuals with cancer histories (N = 43) had not been treated with immune altering medications within the last year. At both Times 1 and 2, cross-sectional main effects were weak or absent for cancer history, perceived stress (e.g. high hassles, low uplifts), and caregiver status; however, interactions occurred between cancer history and perceived stress, such that persons with cancer histories and high hassles/low uplifts had the lowest NKA values (p < .05). These results occurred even after controlling for age, gender, beta-blocker use, hormone replacement therapy, alcohol, and exercise. At Time 1, an interaction also occurred between caregiver status and cancer history--caregivers with cancer histories had lower NKA than did controls with cancer histories and caregivers/controls without cancer histories (p < .05). At Time 2, this interaction only showed a trend (p < .08), primarily because caregivers with cancer histories experienced increases in NKA (p < .05) from Time 1 to Time 2, whereas in the other three groups NKA did not change. Importantly, in caregivers with cancer histories, high perceived stress at Time 1 predicted low NKA at Time 2 (p < .05). This research suggests that the combinations of biological vulnerabilities and chronic/perceived stress may have interactive effects resulting in reduced NKA.

Aged↗
PubMed2007

A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing.

Adult cancers may derive from stem or early progenitor cells. Epigenetic modulation of gene expression is essential for normal function of these early cells but is highly abnormal in cancers, which often show aberrant promoter CpG island hypermethylation and transcriptional silencing of tumor suppressor genes and pro-differentiation factors. We find that for such genes, both normal and malignant embryonic cells generally lack the hypermethylation of DNA found in adult cancers. In embryonic stem cells, these genes are held in a 'transcription-ready' state mediated by a 'bivalent' promoter chromatin pattern consisting of the repressive mark, histone H3 methylated at Lys27 (H3K27) by Polycomb group proteins, plus the active mark, methylated H3K4. However, embryonic carcinoma cells add two key repressive marks, dimethylated H3K9 and trimethylated H3K9, both associated with DNA hypermethylation in adult cancers. We hypothesize that cell chromatin patterns and transient silencing of these important regulatory genes in stem or progenitor cells may leave these genes vulnerable to aberrant DNA hypermethylation and heritable gene silencing during tumor initiation and progression.

Adult↗
PubMed1999

Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal.

Features that distinguish tumor vasculatures from normal blood vessels are sought to enable the destruction of preformed tumor vessels. We show that blood vessels in both a xenografted tumor and primary human tumors contain a sizable fraction of immature blood vessels that have not yet recruited periendothelial cells. These immature vessels are selectively obliterated as a consequence of vascular endothelial growth factor (VEGF) withdrawal. In a xenografted glioma, the selective vulnerability of immature vessels to VEGF loss was demonstrated by downregulating VEGF transgene expression using a tetracycline-regulated expression system. In human prostate cancer, the constitutive production of VEGF by the glandular epithelium was suppressed as a consequence of androgen-ablation therapy. VEGF loss led, in turn, to selective apoptosis of endothelial cells in vessels devoid of periendothelial cells. These results suggest that the unique dependence on VEGF of blood vessels lacking periendothelial cells can be exploited to reduce an existing tumor vasculature.

Androgens↗
PubMedDate not supplied

B-vitamin status and intake in European adolescents. A review of the literature.

BACKGROUND: National and international recommendations for the intake of B vitamins in adolescents consist of estimates and extrapolations from adult values. Due to increasing growth and therefore relatively high energy and nutrient requirements adolescents are a vulnerable group from the nutritional point of view. In addition, a deficient intake of several B vitamins is strongly connected with the development of cancer, neural tube defects and cardiovascular diseases. OBJECTIVE: The aim of this work is to assess dietary intake and status of B vitamins and homocysteine of European adolescents on the basis of published data. METHODS: The database Medline (www.ncvi.nlm.nih.gov) was searched for terms like "Vitamin B", "homocysteine", "Europe", etc. Studies published between June 1980 and December 2004 were analysed for this review. Results of the intake of B vitamins were compared with the EAR or AI, respectively, as recommended by the U.S. Institute of Medicine. Due to lacking reference values for adolescents results of blood status as well as homocysteine were compared to different thresholds for adults. RESULTS: Considering the limitations of the comparability between the reviewed studies e.g. by different methodologies, sample size, age groups, the average intake of B vitamins surpassed the EAR and AI. Boys were better supplied with B vitamins than girls. The intake decreased with increasing age in both genders. A possible deficiency of folate was noticed and girls in particular seemed to be more at risk. Clear regional tendencies for the vitamin intake could not be observed. Results of vitamin B6, B12, folate in blood, and homocysteine were levelled in-between the thresholds. Though the great standard deviation of folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance. folate increased the probability of a deficient supply in parts of the population. CONCLUSIONS: European girls seem to be at risk of folate deficiency. Supplements and fortified food were not taken into consideration by most of the published studies which additionally distorts the real intake. Standardized methods of dietary surveys and reference values for B vitamins as well as homocysteine still must be established. Hence, further investigations are of great relevance.

Adolescent↗
PubMed2006

[Suicidal crisis in oncology: assessment and care].

Patients with advanced cancer often experience with physical impairment and loss of autonomy sometimes preceding inexorable death. It is that can emerge Suicidal ideation occasionally associated with suicidal attempt can arise in this particular context but also following the initial diagnostic talk and during all the stages of the disease. The risk is often considered twice higher in this patients'group compared to the general population and increases with advanced stages of the disease. Among patients with cancer, suicidal crisis can be expressed as part of a request for euthanasia, physician-assisted suicide and para suicide behaviors. Clues can help the clinician to identify early these vulnerable patients. Therefore, suicidal situations can emerge in the particular context of physical impairment, poor quality of life and poor control of physical symptoms (such as pain, tumoral localization in particular lung, head and neck, pancreas). The association of hopelessness and helplessness and a loss of control of the situation are strongly correlated with the expression of suicidal ideations. The presence of a confusional or psychomotor disinhibition with hallucinations, irrational thoughts and the absence of a libidinal object of investment have also to be taken into account. This suicidal crisis can be considered as a way for the patient to escape an intolerable situation (uncontrolled pain or other symptoms) and maintain self-control and decisional autonomy. Management of suicidal crisis in patients with cancer includes careful attention and legitimization of the patient's distress without inducing any guilt. Appropriate control of physical symptoms is warranted including screening and treating any mood disorder or any organic mental disorder. Treating associated anxiety and making sure that the patient's safety is under control are essential. Last but not the least, involving the whole treatment team is key in preventing transformation of the suicidal crisis into institutional crisis.

Body Image↗
PubMed2006

Protein kinases, their function and implication in cancer and other diseases.

Protein phosphorylation is known to play an important role in various cellular processes such as cell division, metabolism, survival and apoptosis. It is driven by specific enzymes, tyrosine and serine-threonine protein kinases. Human protein kinases constitute a complicated system with intricate internal and external interactions. The complexity and sophistication of the system implies its vulnerability. Alterations in functions of these enzymes may launch series of pathological changes within the cell and as a result cause diseases. Protein kinases have been shown to be involved in various pathological processes, first of all malignancies. Deregulation of different protein kinases has been found in chronic myelogenous leukaemia, gastrointestinal stromal tumours, various other sarcomas and cancers as well as non-malignant disorders. Therefore, they are regarded as important effectors in human pathology and represent prospective therapeutic targets.

Animals↗
PubMed2001

Mammography rescreening among older California women.

This is the first study to focus on Medicare mammography rescreening using a relatively large population of older women over a long followup period. To assess correlates of regular mammography, we followed all women age 65 or over enrolled continuously in Medicare fee-for-service (FFS) (n = 515,746) over a 7-year period. Data were drawn from the CMS claims data for the period 1992-1998. Irregular mammography intervals were more commonly found among vulnerable Medicare subpopulations--women who were older, minority, living in low income and lower education areas, and who were enrolled in both Medicare and Medicaid. Health care providers must communicate clearly to older women the breast cancer rescreening message: Not just once, but for a lifetime.

Aged↗
PubMed1979

Adaptation of siblings to childhood malignancy.

To explore the impact of childhood cancer, school-aged patients and their healthy siblings from 71 families were given one or more of the following psychologic tests: the Piers-Harris Children's Self-Concept Scale, the Bene-Anthony Family Relations Test, and the Thematic Apperception Test. The siblings showed even more distress than the patients in the areas of perceived social isolation, perception of their parents as overindulgent and overprotective of the sick child, fear of confronting family members with negative feelings, and concern with failure (older siblings only). In other areas, such as anxiety and vulnerability to illness and injury, the patients' and siblings' experience appeared very similar. These results indicate that siblings, like patients, experience severe stress when confronted with a chronic, life-threatening illness such as cancer. In recognizing and attending to their needs, one can practice primary prevention in pediatrics by facilitating their healthy adaptation to a very difficult situation.

Adaptation, Psychological↗
PubMed2026

Lactylome Reprogramming Mediates Therapeutic Response and Adaptation to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) exhibits high prevalence in China and poor prognosis despite neoadjuvant chemotherapy (NACT), with significant chemoresistance development. Tumor-associated metabolic reprogramming and NACT-induced cellular stress promote lactate accumulation, which serves as a precursor for lysine lactylation (Kla), a post-translational modification potentially regulating cancer progression. We hypothesized that systematic characterization of the lactylome in response to NACT could reveal critical molecular mechanisms underlying treatment and identify new therapeutic vulnerabilities in ESCC. Herein, through comprehensive proteomic and lactylome profiling of tumor and adjacent normal adjacent tissues from 31 ESCC patients (with or without NACT treatment), we identified 8281 proteins and 1836 Kla sites across 62 samples. NACT induced substantial lactylome alterations with 307 differentially expressed Kla sites predominantly in nonhistone proteins involved in DNA damage response and metabolic pathways. Our data revealed that while NACT-induced suppression of energy metabolism, coupled with upregulated 3-hydroxy-3-methylglutaryl reductase degradation 1 complex expression, may exert potential proapoptotic effects, the activation of ribosome biogenesis and increased nucleoprotein lactylation triggered tumor-protective mechanisms. Mechanistically, we demonstrated that DNA damage and elevated lactate levels induced poly(ADP-ribose) polymerase 1 K654 lactylation, enhancing its enzymatic activity and augmenting poly(ADP-ribosyl)ation of downstream targets, potentially playing a pivotal role in chemotherapy resistance-associated pathways. This comprehensive tissue-level landscape of Kla dynamics in ESCC response to chemotherapy establishes Kla as a critical regulatory mechanism in treatment response, potentially offering novel therapeutic targets and predictive biomarkers for personalized treatment strategies.

Humans↗