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Since the 1956 hypothesis of Otto Warburg, aerobic glycolysis has been recognized as a metabolic hallmark of cancer. Because methylglyoxal (MG) is a naturally occurring waste metabolite of glycolysis, we measured blood levels of this molecule in colon cancer-bearing rats. To compare the blood levels of free MG in cancerous and healthy animals,the present study used a dedicated tumor graft model consisting of the subcutaneous administration in syngenic BD-IX rats of a tumorigenic cell clone (PROb) and another non-tumorigenic clone (REGb) derived from the same tumor. Rats grafted with the PROb growing tumor cell clone exhibited a statistically significant increase in free MG blood levels (P=0.003), whereas rats transplanted with the REGb non-growing tumor cell clone exhibited normal MG values. The present study (first of three parts) suggests that cancer cells can produce and release free MG at higher levels than normal cells, making MG a putative novel metabolic biomarker of cancer.

Much of the controversy over the cause of electrohypersensitivity (EHS) lies in the absence of recognized clinical and biological criteria for a widely accepted diagnosis. However, there are presently sufficient data for EHS to be acknowledged as a distinctly well-defined and objectively characterized neurologic pathological disorder. Because we have shown that 1) EHS is frequently associated with multiple chemical sensitivity (MCS) in EHS patients, and 2) that both individualized disorders share a common pathophysiological mechanism for symptom occurrence; it appears that EHS and MCS can be identified as a unique neurologic syndrome, regardless their causal origin. In this overview we distinguish the etiology of EHS itself from the environmental causes that trigger pathophysiological changes and clinical symptoms after EHS has occurred. Contrary to present scientifically unfounded claims, we indubitably refute the hypothesis of a nocebo effect to explain the genesis of EHS and its presentation. We as well refute the erroneous concept that EHS could be reduced to a vague and unproven "functional impairment". To the contrary, we show here there are objective pathophysiological changes and health effects induced by electromagnetic field (EMF) exposure in EHS patients and most of all in healthy subjects, meaning that excessive non-thermal anthropogenic EMFs are strongly noxious for health. In this overview and medical assessment we focus on the effects of extremely low frequencies, wireless communications radiofrequencies and microwaves EMF. We discuss how to better define and characterize EHS. Taken into consideration the WHO proposed causality criteria, we show that EHS is in fact causally associated with increased exposure to man-made EMF, and in some cases to marketed environmental chemicals. We therefore appeal to all governments and international health institutions, particularly the WHO, to urgently consider the growing EHS-associated pandemic plague, and to acknowledge EHS as a mainly new real EMF causally-related pathology.

Since 2009, we built up a database which presently includes more than 2000 electrohypersensitivity (EHS) and/or multiple chemical sensitivity (MCS) self-reported cases. This database shows that EHS is associated in 30% of the cases with MCS, and that MCS precedes the occurrence of EHS in 37% of these EHS/MCS-associated cases. EHS and MCS can be characterized clinically by a similar symptomatic picture, and biologically by low-grade inflammation and an autoimmune response involving autoantibodies against O-myelin. Moreover, 80% of the patients with EHS present with one, two, or three detectable oxidative stress biomarkers in their peripheral blood, meaning that overall these patients present with a true objective somatic disorder. Moreover, by using ultrasonic cerebral tomosphygmography and transcranial Doppler ultrasonography, we showed that cases have a defect in the middle cerebral artery hemodynamics, and we localized a tissue pulsometric index deficiency in the capsulo-thalamic area of the temporal lobes, suggesting the involvement of the limbic system and the thalamus. Altogether, these data strongly suggest that EHS is a neurologic pathological disorder which can be diagnosed, treated, and prevented. Because EHS is becoming a new insidious worldwide plague involving millions of people, we ask the World Health Organization (WHO) to include EHS as a neurologic disorder in the international classification of diseases.

Exposure to low frequency and radiofrequency electromagnetic fields at low intensities poses a significant health hazard that has not been adequately addressed by national and international organizations such as the World Health Organization. There is strong evidence that excessive exposure to mobile phone-frequencies over long periods of time increases the risk of brain cancer both in humans and animals. The mechanism(s) responsible include induction of reactive oxygen species, gene expression alteration and DNA damage through both epigenetic and genetic processes. In vivo and in vitro studies demonstrate adverse effects on male and female reproduction, almost certainly due to generation of reactive oxygen species. There is increasing evidence the exposures can result in neurobehavioral decrements and that some individuals develop a syndrome of "electro-hypersensitivity" or "microwave illness", which is one of several syndromes commonly categorized as "idiopathic environmental intolerance". While the symptoms are non-specific, new biochemical indicators and imaging techniques allow diagnosis that excludes the symptoms as being only psychosomatic. Unfortunately standards set by most national and international bodies are not protective of human health. This is a particular concern in children, given the rapid expansion of use of wireless technologies, the greater susceptibility of the developing nervous system, the hyperconductivity of their brain tissue, the greater penetration of radiofrequency radiation relative to head size and their potential for a longer lifetime exposure.

Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called “provocation tests”, which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF). However, because those tests depend on multiple EMF-associated physical and biological parameters and have been conducted in patients without having first defined EHS objectively and/or endpoints adequately, they cannot presently be considered to be valid pathogenesis research methodologies. Consequently, the negative results obtained by these tests do not preclude a role of EMF exposure as a symptomatic trigger in EHS patients. Moreover, there is no proof that EHS symptoms or EHS itself are caused by psychosomatic or nocebo effects. This international consensus report pleads for the acknowledgement of EHS as a distinct neuropathological disorder and for its inclusion in the WHO International Classification of Diseases.

A total of 32 electrohypersensitivity (EHS) self-reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid-reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite-induced oxidative/nitrosative stress. In addition, the activity of Cu-Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30–50% of EHS self-reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P

Metabolic syndrome and type 2 diabetes are associated with increased risk of breast cancer development and progression. Methylglyoxal (MG), a glycolysis by-product, is generated through a non-enzymatic reaction from triose-phosphate intermediates. This dicarbonyl compound is highly reactive and contributes to the accumulation of advanced glycation end products. In this study, we analyzed the accumulation of Arg-pyrimidine, a MG-arginine adduct, in human breast adenocarcinoma and we observed a consistent increase of Arg-pyrimidine in cancer cells when compared with the non-tumoral counterpart. Further immunohistochemical comparative analysis of breast cancer subtypes revealed that triple negative lesions exhibited low accumulation of Arg-pyrimidine compared with other subtypes. Interestingly, the activity of glyoxalase 1 (Glo-1), an enzyme that detoxifies MG, was significantly higher in triple negative than in other subtype lesions, suggesting that these aggressive tumors are able to develop an efficient response against dicarbonyl stress. Using breast cancer cell lines, we substantiated these clinical observations by showing that, in contrast to triple positive, triple negative cells induced Glo-1 expression and activity in response to MG treatment. This is the first report that Arg-pyrimidine adduct accumulation is a consistent event in human breast cancer with a differential detection between triple negative and other breast cancer subtypes.

A careful molecular biology, epidemiological and mathematical modelling reanalysis of the recently published study titled 'Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions' by Cristian Tomasetti and Bert Vogelstein, which was published on January 2, 2015 in the distinguished journal Science, led to the conclusion that, contrary to the authors' claim, many cancer types are not caused by replicative random mutations. Rather than the authors' two arbitrarily individualized groups of cancer, a three-group model is herein proposed in the framework of this technical comment, considerably reducing the fraction of cancer cases hypothetically attributable to random mutations.

Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion. Elevated MG levels resulted in sustained YAP nuclear localization/activity that could be reverted using Carnosine, a scavenger for MG. MG treatment affected Hsp90 chaperone activity and decreased its binding to LATS1, a key kinase of the Hippo pathway. Cancer cells with high MG stress showed enhanced growth and metastatic potential in vivo. These findings reinforce the cumulative evidence pointing to hyperglycemia as a risk factor for cancer incidence and bring renewed interest in MG scavengers for cancer treatment. DOI: http://dx.doi.org/10.7554/eLife.19375.001

The classical view according to which overweight/obesity is related to cancer considers adipose tissue as an active and metabolic "organ", acting through endocrine, autocrine and paracrine processes. Consequently, it has been hypothesized, that genesis and progression of cancer may be caused by different biological factors acting through diverse mechanisms including changes in the synthesis and bioavailability of sex hormones, insulin resistance, release of growth factors and/or proinflammatory cytokines and abnormal energetic disposal and expenditure. We have shown that overweight/obesity can be experimentally induced by benzo[a]pyrene, a universal well characterized chemical pollutant and that overweight/obesity may in fact be caused by several types of chemical pollutants. In this paper we propose that in addition to the above hypothetical biological mechanisms, adipose tissue acts as a reservoir for lipophilic, liposoluble environmental carcinogens, so that chemical pollution may in fact generate both overweight/obesity and cancer. More precisely, we propose that many carcinogens, be they mutagens or promotors can be stored in the adipose tissue, be released at convenient dose in the blood circulation and therefore target peripheral tissues to induce carcinogenesis. Such carcinogens mainly include organochlorine pesticides and PCBs. Their association with an increased risk of cancer seems to be demonstrated for breast and prostate carcinoma, as well as for lymphoma, not only in obese patients, but also in normal weight or even leaner patients suggesting that the adipose tissue may act as a reservoir for environmental carcinogens in obese as well as in non-obese patients.

The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed. (1) Over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased in Western Europe and North America. (2) Obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other known lifestyle-related factors. (3) There is evidence that the environment has changed over the time period preceding the recent rise in cancer incidence, and that this change, still continuing, included the accumulation of many new carcinogenic factors in the environment. (4) Genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions. (5) Age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children, and adolescents. (6) The fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical time window may explain why current epidemiological studies may still be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment, including microorganisms (viruses, bacteria and parasites), radiations (radioactivity, UV and pulsed electromagnetic fields) and many xenochemicals, may account for the recent growing incidence of cancer and therefore that the risk attributable to environmental carcinogen may be far higher than it is usually agreed. Of major concern are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children and food contamination by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and some ingredients and contaminants in cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

Much of the controversy over the causes of electro-hypersensitivity (EHS) and multiple chemical sensitivity (MCS) lies in the absence of both recognized clinical criteria and objective biomarkers for widely accepted diagnosis. Since 2009, we have prospectively investigated, clinically and biologically, 1216 consecutive EHS and/or MCS-self reporting cases, in an attempt to answer both questions. We report here our preliminary data, based on 727 evaluable of 839 enrolled cases: 521 (71.6%) were diagnosed with EHS, 52 (7.2%) with MCS, and 154 (21.2%) with both EHS and MCS. Two out of three patients with EHS and/or MCS were female; mean age (years) was 47. As inflammation appears to be a key process resulting from electromagnetic field (EMF) and/or chemical effects on tissues, and histamine release is potentially a major mediator of inflammation, we systematically measured histamine in the blood of patients. Near 40% had a increase in histaminemia (especially when both conditions were present), indicating a chronic inflammatory response can be detected in these patients. Oxidative stress is part of inflammation and is a key contributor to damage and response. Nitrotyrosin, a marker of both peroxynitrite (ONOO°-) production and opening of the blood-brain barrier (BBB), was increased in 28% the cases. Protein S100B, another marker of BBB opening was increased in 15%. Circulating autoantibodies against O-myelin were detected in 23%, indicating EHS and MCS may be associated with autoimmune response. Confirming animal experiments showing the increase of Hsp27 and/or Hsp70 chaperone proteins under the influence of EMF, we found increased Hsp27 and/or Hsp70 in 33% of the patients. As most patients reported chronic insomnia and fatigue, we determined the 24 h urine 6-hydroxymelatonin sulfate (6-OHMS)/creatinin ratio and found it was decreased (

Metabolic disorders influence breast cancer development and progression. Methylglyoxal (MGX), is a highly reactive glycolytic byproduct able to inflict carbonyl stress to proteins, lipids and DNA. The possible role of MGX in breast cancer development has not been yet extensively explored. We analyzed the accumulation of Arg-pyrimidine adducts, in a series of more than 100 human breast adenocarcinoma and we observed a consistent increased of MGX adducts in cancer cells compared to the non-tumoral counterpart. Most triple negative lesions examined exhibited low accumulation of Arg-pyrimidine residues compared other subtypes. Intriguingly, the level of expression of glyoxalase 1 (Glo-1), an enzyme that detoxifies MGX, was similar in both triple negative and other subtype lesions, suggesting a potential difference in the Glo-1 activity. This hypothesis is supported by our preliminary results on breast cancer cell lines, showing that triple negative cells are more efficient to respond to treatment with MGX by ...

A total of 35 patients with advanced cancer and severe pain not controllable by step 2 analgesics (according to WHO criteria) were included in this double-blind study. No patients were receiving concomitant oncological treatment. During a stabilisation period, all patients received sufficient morphine sulfate 5 mg/ml syrup every 4 hours to achieve a satisfactory level of pain relief (60 to 300 mg/day). The patients were then randomised to receive the same dosage of morphine sulfate 5 mg/ml syrup every 4 hours or sustained release (SR) morphine sulfate (as 30 or 60mg capsules) every 12 hours for 6 days, according to a double-blind crossover design. Analgesic efficacy was assessed daily with a visual analogue scale and a 5-point verbal rating scale. At the end of each treatment period, morphine plasma concentrations at steady-state were measured by high performance liquid chromatography. There were no differences between the 2 formulations in terms of subjective analgesic efficacy (measured at 10am, 2pm, 6pm and 10pm) among 20 evaluable patients. Overall, the incidence of opiate-related adverse events was similar with both formulations, and no unexpected adverse events were reported. Mean (± SD) pharmacokinetic parameters assessed in 25 patients were as follows: the maximum plasma concentration was 49.5 ± 28.4 µg/L for morphine syrup vs 48.1 ± 30.7 for the SR capsules [90% confidence interval (CI) 86.8 to 114.0%]; and the area under the concentration-time curve from zero to 12 hours (AUC12h) was 308.4 ± 203.8 µg/L·h for the syrup vs 323 ± 201.7 for the capsules (90% CI 99.1 to 124.5%). There was a linear relationship between the daily dose of morphine and AUC12h. The results of this study suggest that equal dosages of morphine as SR capsules (containing 30 or 60mg morphine) given 12-hourly and morphine 5 mg/ml syrup given 4-hourly are bioequivalent. Furthermore, the 2 formulations are equally effective and well tolerated in the treatment of severe pain in patients with cancer.

Background. The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question. Methods. From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients). Results. The sex ratio (M :F) was 19/1 ; mean age was 57 ± 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival. Conclusions. The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients. Cancer 1995 ; 76 :779-86.

We have previously shown that benzo[a]pyrene (B[a]P) administrated at extremely low dose can cause weight gain in mice and that the increase in adipose tissue mass is due to inhibition of beta-adrenergic stimulation of lipolysis. Moreover we have suggested that in addition to its endocrine properties, adipose tissue act as a reservoir for many chemical carcinogens including Polycyclic Aromatic Hydrocarbons (PAHs). In this paper we show that B[a]P as well as the two C4 PAHs, pyrene and phenanthrene can bioaccumulate into adipocytes in a similar manner, but that at the difference of B[a]P, have no impact on epinephrine-induced lipolysis. On the basis of this ex vivo study, we therefore suggest that B[a]P may play a central role in carcinogenesis not only by inducing cancer through its mutagenic properties, but also by increasing the bioaccumulation capacity of the adipose tissue mass.

International audience; We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

PURPOSE Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer. PATIENTS AND METHODS Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival. RESULTS Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), > or = 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the principal side effects were emesis and a transient decrease in blood pressure. CONCLUSION Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.

Twenty-one patients with advanced epidermoid carcinoma of the esophagus were treated with a combination of 5-fluorouracil (F) 600 mg/m2 day 1 and day 8; Adriamycin (A) 30 mg/m2 day 1; and cisplatin (P) 75 mg/m2 day 1 (FAP) with hydration and mannitol-induced diuresis. Each course was repeated every 4 weeks. All 21 patients are evaluable for response: 7 patients had an objective response (33%). Two of these responses were complete remissions according to negative endoscopic and pathologic results; five patients had a partial response; all 7 responding patients had metastasis prior to treatment. Median survival of the 21 patients was 8 months. Median survival of 9 months for responders is superior to 4.5 months for nonresponders. No severe myelosuppression or nephrotoxicity was observed. This FAP regimen is useful in the treatment of advanced esophageal tumors.

The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.

We report two cases of μ—heavy-chain disease. Both patients were affected with a lymphoproliferative disease that shared several suggestive features with the previously reported cases of μ-chain disease: the presence of vacuolated plasma cells in bone marrow, a small amount of α 2 moving abnormal μ-chain protein, and urinary K Bence Jones protein in one case. ( Arch Intern Med 139:672-674, 1979)