Soluble and cell-associated transferrin receptor in lung cancer.

The expression of transferrin receptor (TfR) has been identified in many malignant tumours. In lung cancer, lymphoma and breast cancer, it has been shown that the expression of TfR correlates with tumour differentiation, probably implying some prognostic value. A soluble form of TfR (sTfR) in human serum has been shown to be proportional to the number of cellular TfRs. Based on these data we examined the utility of measuring sTfR in the serum and bronchoalveolar lavage (BAL) fluid of patients with lung cancer (n = 32) and patients with chronic obstructive pulmonary disease (n = 22). BAL fluid was centrifuged to separate the supernatant from the cellular component. Cells were lysed in a detergent and cell-associated TfR was measured by enzyme-linked immunosorbent assay (ELISA) and expressed as ng 10(-6) cells in this cellular component. There was no difference in serum sTfR between the cancer and chronic obstructive pulmonary disease (COPD) groups. A higher level of cell-associated TfR was found in BAL of non-small-cell lung cancer patients than in COPD patients (P = 0.01). The calculated number of TfR molecules per cell in BAL correlated positively with the percentage of macrophages in BAL (P < 0.0001), suggesting that cell-associated TfR in BAL originates primarily from macrophages in this fluid. No correlation existed between BAL cell-associated TfR and tumour size, nodal status, the presence of metastases and serum sTfR. BAL cell-associated TfR was negatively correlated with BAL supernatant neuron-specific enolase (NSE) (P = 0.01). A combination of BAL supernatant NSE and cell-associated TfR detected lung cancer with a sensitivity of 91%, a specificity of 59% and positive and negative predictive values of 81% and 71% respectively. In conclusion, BAL cell-associated TfR may help in the differential diagnosis of lung cancer vs pneumonia

Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study

Background Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. Patients and methods We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. Results Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P=0.0015), while BCL2 expression predicted a worse OS (P=0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P=0.03). Conclusions WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpar

Perinatal fluoxetine increases hippocampal neurogenesis and reverses the lasting effects of pre-gestational stress on serum corticosterone, but not on maternal behavior, in the rat dam

There is increasing evidence that mental health concerns, stress-related mental illnesses, and parental stress prior to conception have long-term effects on offspring outcomes. However, more work is needed to understand how pre-gestational stress might affect neurobehavioral outcomes in the mother. We investigated how chronic stress prior to gestation affects maternal behavior and related physiology, and aimed to determine the role that perinatal SSRIs have in altering these stress effects. To do this, female Sprague-Dawley rats were subject to chronic unpredictable stress (CUS) prior to breeding. During the perinatal period they were administered fluoxetine (10 mg/kg/day). Four groups of dams were studied: Control + Vehicle, Pre-gestational Stress + Vehicle, Control + Fluoxetine and Pre-gestational Stress + Fluoxetine. Maternal weight, breeding success, and maternal caregiving behaviors were recorded. Measures of serum corticosterone and corticosteroid-binging globulin (CBG) and the number of immature neurons in the dorsal hippocampus were also assessed in the late postpartum. Main findings show pre-gestational stress resulted in poor reproductive success and maintenance of pregnancy. Pre-gestationally stressed dams also showed higher levels of nursing and fewer bouts of licking/grooming offspring in the first week postpartum – behaviors that were not reversed by perinatal fluoxetine treatment. In the dam, perinatal fluoxetine treatment reversed the effect of pre-gestational maternal stress on serum corticosterone levels and increased serum CBG levels as well as neurogenesis in the dorsal hippocampus. Maternal corticosterone levels significantly correlated with blanket and passive nursing. This work provides evidence for a long-term impact of stress prior to gestation in the mother, and shows that perinatal SSRI medications can prevent some of these effects. © 2017 Elsevier B.V

Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis. Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease. Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia. Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1)

Long-term follow-up of patients treated with radiotherapy alone for early-stage histologically aggressive non-Hodgkin's lymphoma

Historically localised aggressive non-Hodgkin's lymphoma (NHL) has been treated with involved field radiotherapy (RT), chemotherapy, or a combination of both modalities. The current weight of evidence supports a preference for combined modality treatment (CMT). Increased patient age at diagnosis is well recognised as a poor prognostic indicator in NHL, but despite this some perceive CMT as too toxic for use in the elderly. As a result, some older patients continue to be offered RT alone. Here, we present long-term follow-up of 377 adults of all ages treated with RT alone for early-stage diffuse large-cell lymphoma on British National Lymphoma Investigation trials between 1974 and 1997. 10-year cause-specific survival in patients older than 60 years was poor and significantly inferior to that in younger patients (47 and 75% respectively; P<0.001). There is growing evidence that short-course chemotherapy, with or without RT, is superior to RT alone in early-stage aggressive NHL, in elderly as well as in younger patients. Increased age alone should not exclude patients from systemic treatment for early-stage aggressive NHL