Tag: cancer

Of Mice and Men: On the Origin of XMRV

Abstract:

The novel human retrovirus xenotropic murine leukemia virus-related virus (XMRV) is arguably the most controversial virus of this moment. After its original discovery in prostate cancer tissue from North American patients, it was subsequently detected in individuals with chronic fatigue syndrome from the same continent. However, most other research groups, mainly from Europe, reported negative results.

The positive results could possibly be attributed to contamination with mouse products in a number of cases, as XMRV is nearly identical in nucleotide sequence to endogenous retroviruses in the mouse genome. But the detection of integrated XMRV proviruses in prostate cancer tissue proves it to be a genuine virus that replicates in human cells, leaving the question: how did XMRV enter the human population?

We will discuss two possible routes: either via direct virus transmission from mouse to human, as repeatedly seen for, e.g., Hantaviruses, or via the use of mouse-related products by humans, including vaccines. We hypothesize that mouse cells or human cell lines used for vaccine production could have been contaminated with a replicating variant of the XMRV precursors encoded by the mouse genome.

 

Source: van der Kuyl AC, Cornelissen M, Berkhout B. Of Mice and Men: On the Origin of XMRV. Front Microbiol. 2011 Jan 17;1:147. doi: 10.3389/fmicb.2010.00147. ECollection 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109487/ (Full article)

 

A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma

Abstract:

OBJECTIVE: The objective of this study was to simulate changes in the human T cell system representing Canale-Smith syndrome using a dynamic computer model of T cell development and comparing with available human data.

STUDY DESIGN: Physiological stepwise maturation and function of T lymphocytes in the computer model is altered by introducing functional disturbances following lymphotropic virus infection. In the present model, acute and chronic persistent infection with the human herpesvirus-6 (HHV-6) was simulated, and ensuing changes in T cell populations were compared with those measured in human patients.

RESULTS: Using our computer model we previously found that simulated acute HHV-6 infection produced T cell computer data, which resembled an infectious mononucleosis-like disease in patients. Simulated chronic persistent infection, instead, resulted in variable cell changes comparing well to patients with chronic fatigue syndrome. In one setting, however, persistent immature lymphocytosis was observed similar to what initial has been described in this journal as Canale-Smith syndrome.

CONCLUSION: Using a computer model developed by us we were able to produce simulations that resemble the immune system features of Canale-Smith syndrome. Further understanding of these simulation results may possibly guide future investigations into this disorder.

 

Source: Krueger GR, Brandt ME, Wang G, Berthold F, Buja LM. A computational analysis of Canale-Smith syndrome: chronic lymphadenopathy simulating malignant lymphoma. Anticancer Res. 2002 Jul-Aug;22(4):2365-71. http://www.ncbi.nlm.nih.gov/pubmed/12174928

 

Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome

Abstract:

The goal of our work was to assess fatigue in disease-free cancer patients with help of a validated fatigue questionnaire. Furthermore, we wished to analyse the relationship between severe fatigue and former treatment modalities, problems of concentration and motivation, physical activity, functional impairment, depression and anxiety and finally, to compare severely fatigued disease-free cancer patients and patients with Chronic Fatigue Syndrome (CFS).

The participants were 85 adult cancer patients and 16 patients with CFS. The cancer patients were all disease-free and had been off treatment for a minimum of 6 months. They were asked to participate in this study by their physician when they came to the hospital for control visits. Patients who were willing to participate completed four questionnaires. The Checklist Individual Strength was used to measure fatigue. In addition, the Beck Depression Inventory, the Spielberger Trait Anxiety Inventory and the Nottingham Health Profile were used.

Results indicate that 19% of the disease-free cancer patients were severely fatigued. Their fatigue experience is comparable to that of patients with CFS. Severe fatigue is associated with problems of concentration and motivation, reduced physical activity, emotional health problems and pain.

Furthermore, a relation was found between fatigue and depression and anxiety. No relation was found between fatigue and type of cancer, former treatment modalities, duration of treatment and time since treatment ended. In conclusion, for one fifth of a group of disease-free cancer patients fatigue is a severe problem long after treatment. In addition to fatigue, these patients experience several psychological and physical problems.

 

Source: Servaes P, van der Werf S, Prins J, Verhagen S, Bleijenberg G. Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome. Support Care Cancer. 2001 Jan;9(1):11-7. http://www.ncbi.nlm.nih.gov/pubmed/11147137

 

Chronic fatigue syndrome in private practice psychiatry: family history of physical and mental health

Abstract:

Forty-five psychiatric patients with chronic fatigue syndrome (CFS) were compared, using the case-control method, to two control groups selected from the same practice and matched on age, gender, and psychiatric diagnosis.

The first control group (C-I, N=90) was selected on the basis of relatively good physical health. The second control group (C-II, N=45) was selected without regard to physical health. The reported family history of physical health revealed: the CFS mothers died at a younger age than the C-II mothers; both parents died before age 65 among the CFS parents more frequently than did the C-I parents; and the CFS parents had an increased prevalence of cancer, autoimmune disorders, and CFS-like conditions as compared to the families of one or both control groups.

The reported family history of mental disorders revealed no significant differences in any of these conditions between the CFS patients and either control group.

 

Source: Endicott NA. Chronic fatigue syndrome in private practice psychiatry: family history of physical and mental health. J Psychosom Res. 1999 Oct;47(4):343-54. http://www.ncbi.nlm.nih.gov/pubmed/10616228

 

Dysfunction of natural killer activity in a family with chronic fatigue syndrome

Abstract:

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention.

Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry.

NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood.

Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

 

Source: Levine PH, Whiteside TL, Friberg D, Bryant J, Colclough G, Herberman RB. Dysfunction of natural killer activity in a family with chronic fatigue syndrome. Clin Immunol Immunopathol. 1998 Jul;88(1):96-104. http://www.ncbi.nlm.nih.gov/pubmed/9683556

 

Cancer and a fatiguing illness in Northern Nevada–a causal hypothesis

Abstract:

PURPOSE: We investigated the possibility that chronic fatigue syndrome (CFS) predisposes to cancer by comparing the cancer pattern in an area in northern Nevada, where an outbreak of a fatiguing illness, which included cases of CFS, was reported, to an area in southern Nevada, where no such illness was reported.

METHODS: Data from the computerized Nevada Cancer Registry were utilized to compare incidence rates of four malignancies–brain cancer, non-Hodgkin lymphoma (NHL), lung cancer, and breast cancer–in Washoe and Lyon Counties, where an unexplained fatiguing illness was reported during 1984-86, with comparably sized Clark County, where no such illness was reported.

RESULTS: Higher incidences of NHL and primary brain tumors were noted in the two northern Nevada counties (Washoe and Lyon) in 1986 and 1987 respectively, compared to the southern Nevada (Clark) county. Similar patterns were not seen for breast or lung cancer.

CONCLUSIONS: This study provides a model for investigating the possible predisposition of CFS patients to develop cancer using other cohorts, but it is currently premature to accept such a link at this time.

 

Source: Levine PH, Fears TR, Cummings P, Hoover RN. Cancer and a fatiguing illness in Northern Nevada–a causal hypothesis. Ann Epidemiol. 1998 May;8(4):245-9. http://www.ncbi.nlm.nih.gov/pubmed/9590603

 

An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry

Abstract:

Chronic fatigue syndrome (CFS) has been increasingly associated with immune dysregulation, including depressed natural killer cell activity; this phenomenon is associated with increased susceptibility to cancer. Although anecdotal reports have suggested an association between CFS and cancer, particularly non-Hodgkin’s lymphoma and brain cancer, there has been no a priori justification for evaluating such an association and no consideration of relevant parameters, such as length of latent period vs. tumor type.

We reviewed data from the Nevada State Cancer Registry subsequent to a reported outbreak of a CFS-like illness in Nevada that occurred during 1984-1986. We concentrated on non-Hodgkin’s lymphoma and brain/CNS tumors, with particular emphasis on persons 15-34 and 35-54 years of age.

An upward trend in the incidence of brain/CNS tumors, which could be related to a national upward trend for this disease, was noted. No consistent trends were noted for non-Hodgkin’s lymphoma.

Because of the difficulties inherent in studies of cancer subsequent to various exposures, we evaluated the methodology for determining an association between outbreaks of CFS-like disease and cancer. We propose several approaches that should be considered in future studies for investigation of possible associations between CFS and cancer, including expected latent periods for specific tumors.

 

Source: Levine PH, Atherton M, Fears T, Hoover R. An approach to studies of cancer subsequent to clusters of chronic fatigue syndrome: use of data from the Nevada State Cancer Registry. Clin Infect Dis. 1994 Jan;18 Suppl 1:S49-53. http://www.ncbi.nlm.nih.gov/pubmed/8148453

 

Does chronic fatigue syndrome predispose to non-Hodgkin’s lymphoma?

Abstract:

Chronic fatigue syndrome, an illness that frequently is associated with abnormalities of cellular immunity, has been reported anecdotally to be associated with an increased incidence of lymphoid hyperplasia and malignancy.

This report describes an initial analysis of population-based cancer incidence data in Nevada, focusing on the patterns of non-Hodgkin’s lymphoma prior to and subsequent to well described, documented outbreaks of chronic fatigue syndrome during 1984-1986. In a study of time trends in four age groups, the observed time trends were consistent with the national trends reported in the Surveillance, Epidemiology, and End Results Program.

No statistically significant increase attributable to the chronic fatigue syndrome outbreak was identified at the state level. Additional studies are in progress analyzing the data at the country level, reviewing patterns in other malignancies, and continuing to monitor the cancer patterns over subsequent years.

 

Source: Levine PH, Peterson D, McNamee FL, O’Brien K, Gridley G, Hagerty M, Brady J, Fears T, Atherton M, Hoover R. Does chronic fatigue syndrome predispose to non-Hodgkin’s lymphoma? Cancer Res. 1992 Oct 1;52(19 Suppl):5516s-5518s; discussion 5518s-5521s. http://www.ncbi.nlm.nih.gov/pubmed/1394166

 

alpha-Interferon and 5-fluorouracil: possible mechanisms of antitumor action

Abstract:

We have treated 17 patients with 5-fluorouracil (5-FU, 300 mg/m2/d by continuous ambulatory infusion for 8 weeks) and interferon alfa-2b (escalating doses to cohorts of three to five patients, given subcutaneously on a daily schedule at 2.0, 3.5, 5.0, and 10.0 x 10(6) IU/m2). The two major toxicities observed were mucositis, which occurred in 10 patients at 2 weeks and required interruption of therapy and 5-FU dose reduction, and chronic fatigue syndrome, which required reduction of the dose of interferon alfa-2b.

Other toxicities seen included elevation in BUN/creatinine, elevation in liver function tests, alopecia, diarrhea, confusion, and myelosuppression. No toxic deaths occurred. Five responses were observed: two complete responses, two partial responses, and one minor response, all in patients with gastrointestinal malignancy; three of the responding patients had previously failed 5-FU-containing regimens.

When we measured 5-FU plasma levels in nine of our patients, they were at or below 1 ng/mL in most patients; however, within 1 hour of administration of interferon alfa-2b, plasma levels rose 16-fold. This elevation of 5-FU levels persisted for at least 24 hours, and could not be accounted for on the basis of altered interleukin-6 levels. When the regimen was tested in eight patients with metastatic renal cell carcinoma as part of a pilot study, three partial responses were observed, and no patient developed disease progression while on treatment. The combination of 5-FU, given by continuous infusion, and interferon alfa-2b, given daily, appears worthy of advancement to phase II trials.

 

Source: Meadows LM, Walther P, Ozer H. alpha-Interferon and 5-fluorouracil: possible mechanisms of antitumor action. Semin Oncol. 1991 Oct;18(5 Suppl 7):71-6. http://www.ncbi.nlm.nih.gov/pubmed/1948133