Toward a genetics of cancer resistance

Klein, George

doi:10.1073/pnas.0811616106

Cited by 54 publications

(58 citation statements)

References 49 publications

(40 reference statements)

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“…11 However, this has yet to be converted into new therapeutic approaches. 13 Here we consider what may protect nonclinical voice hearers, inspired by similar studies in addiction, 14 oncology, 15 and infectious diseases 16,17 : there are individuals who are resilient despite similar exposure to risk factors as individuals who become ill.…”

Section: Introductionmentioning

confidence: 99%

Varieties of Voice-Hearing: Psychics and the Psychosis Continuum

Powers

Kelley

Corlett

2016

Schizophrenia Bulletin

106

136

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Hearing voices that are not present is a prominent symptom of serious mental illness. However, these experiences may be common in the non-help-seeking population, leading some to propose the existence of a continuum of psychosis from health to disease. Thus far, research on this continuum has focused on what is impaired in help-seeking groups. Here we focus on protective factors in non-help-seeking voice-hearers. We introduce a new study population: clairaudient psychics who receive daily auditory messages. We conducted phenomenological interviews with these subjects, as well as with patients diagnosed with a psychotic disorder who hear voices, people with a diagnosis of a psychotic disorder who do not hear voices, and matched control subjects (without voices or a diagnosis). We found the hallucinatory experiences of psychic voice-hearers to be very similar to those of patients who were diagnosed. We employed techniques from forensic psychiatry to conclude that the psychics were not malingering. Critically, we found that this sample of nonhelp-seeking voice hearers were able to control the onset and offset of their voices, that they were less distressed by their voice-hearing experiences and that, the first time they admitted to voice-hearing, the reception by others was much more likely to be positive. Patients had much more negative voice-hearing experiences, were more likely to receive a negative reaction when sharing their voices with others for the first time, and this was subsequently more disruptive to their social relationships. We predict that this sub-population of healthy voice-hearers may have much to teach us about the neurobiology, cognitive psychology and ultimately the treatment of voices that are distressing.

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Section: Introductionmentioning

confidence: 99%

Varieties of Voice-Hearing: Psychics and the Psychosis Continuum

Powers

Kelley

Corlett

2016

Schizophrenia Bulletin

106

136

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“…Meanwhile, stress has been shown to be associated with increased levels of cortisol (10) and also immune suppression (11). Immune resistance has been suggested to be chiefly involved in infection-related cancers (12,13). Thus, if any, the impact of stress might be greatest for cancers that have strong indication for infection.…”

Section: Introductionmentioning

confidence: 99%

Risk of Infection-Related Cancers after the Loss of a Child: A Follow-up Study in Sweden

et al. 2011

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It is unknown whether severe emotional stress due to loss of a child influences the risk of cancers susceptible to immune modulation such as infection-related cancers. We conducted a historic cohort study in 1990 to 2004 on the basis of the Swedish Multi-Generation Register including 4,687,073 parents. Death of a child was identified through the Causes of Death Register. Poisson regression was used to derive the relative risks (RR) and 95% confidence intervals (CI) of infection-related cancers, comparing the incidence rates of parents who lost a child with those who never lost a child. A total of 101,306 parents (2%) had lost a child during follow-up, among whom 1,608 subsequently developed infection-related cancers. After adjustment for age, sex, calendar year, educational level, and civil status, the overall RR of 14 cancers studied was 1.07 (95% CI: 1.02-1.12). Parents who lost a child were particularly at a higher risk for cancers potentially associated with human papilloma virus (HPV) infection such as cervical cancer (RR: 1.46; 95% CI: 1.17-1.80). Higher RRs for most cancers were obtained within 5 years after child loss and excess risk for liver and stomach cancers was confined to that period. No association was observed for lymphoma and nonmelanoma skin cancer at any time point after child loss. Although potential confounding by unmeasured factors cannot be ruled out, our findings lend support to the hypothesis that severe life stressors, such as child loss, may raise the risk for several, chiefly HPV-related, cancers. Cancer Res; 71(1); 116-22. Ó2010 AACR.

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“…Developing preneoplastic cells in the process of escaping from their intrinsic checkpoints that prevent illegitimate cell proliferation also have to overcome the microenvironmental forces that maintain the integrity of the normal tissue architecture. It is becoming increasingly clear that the normal microenvironment can restrict cancer development and progression (1)(2)(3). Inhibition of tumor cell growth by normal fibroblasts is one measurable manifestation of this multicomponential control.…”

mentioning

confidence: 99%

“…Part of this process is reflected by the ability of the tumor cell to corrupt the surrounding stroma and turn it from restrictive to supportive. The generation of cancer-associated fibroblasts (CAFs) that enhance angiogenesis and support tumor growth and spreading through the release of growth factors and cytokines is a case in point (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent

Alkasalias

Flaberg

Kashuba

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Normal human and murine fibroblasts can inhibit proliferation of tumor cells when cocultured in vitro. The inhibitory capacity varies depending on the donor and the site of origin of the fibroblast. We showed previously that effective inhibition requires formation of a morphologically intact fibroblast monolayer before seeding of the tumor cells. Here we show that inhibition is extended to motility of tumor cells and we dissect the factors responsible for these inhibitory functions. We find that inhibition is due to two different sets of molecules: (i) the extracellular matrix (ECM) and other surface proteins of the fibroblasts, which are responsible for contact-dependent inhibition of tumor cell proliferation; and (ii) soluble factors secreted by fibroblasts when confronted with tumor cells (confronted conditioned media, CCM) contribute to inhibition of tumor cell proliferation and motility. However, conditioned media (CM) obtained from fibroblasts alone (nonconfronted conditioned media, NCM) did not inhibit tumor cell proliferation and motility. In addition, quantitative PCR (Q-PCR) data show upregulation of proinflammatory genes. Moreover, comparison of CCM and NCM with an antibody array for 507 different soluble human proteins revealed differential expression of growth differentiation factor 15, dickkopf-related protein 1, endothelial-monocyteactivating polypeptide II, ectodysplasin A2, Galectin-3, chemokine (C-X-C motif) ligand 2, Nidogen1, urokinase, and matrix metalloproteinase 3.tumor microenvironment | cancer-associated fibroblast | motility | extracellular matrix | soluble factors T he normal balance between epithelial cells and the surrounding stroma is disrupted during tumor development. Developing preneoplastic cells in the process of escaping from their intrinsic checkpoints that prevent illegitimate cell proliferation also have to overcome the microenvironmental forces that maintain the integrity of the normal tissue architecture. It is becoming increasingly clear that the normal microenvironment can restrict cancer development and progression (1-3). Inhibition of tumor cell growth by normal fibroblasts is one measurable manifestation of this multicomponential control. Part of this process is reflected by the ability of the tumor cell to corrupt the surrounding stroma and turn it from restrictive to supportive. The generation of cancer-associated fibroblasts (CAFs) that enhance angiogenesis and support tumor growth and spreading through the release of growth factors and cytokines is a case in point (1-5).We have departed from the observation of Stoker et al. that normal fibroblasts can inhibit the growth of admixed tumor cells upon contact (6). Having confirmed their findings, we have extended such findings into a high throughput microwell system and showed that the strength of the inhibition differs depending on the source of the fibroblasts. Moreover, such inhibition is contact dependent as well as requires an intact fibroblast monolayer (7, 8).Here we report the surprising finding that the inhi...

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Toward a genetics of cancer resistance

Cited by 54 publications

References 49 publications

Varieties of Voice-Hearing: Psychics and the Psychosis Continuum

Varieties of Voice-Hearing: Psychics and the Psychosis Continuum

Risk of Infection-Related Cancers after the Loss of a Child: A Follow-up Study in Sweden

Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent

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