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In many tumors, CD73 (NT5E), a rate-limiting enzyme in adenosine biosynthesis, is upregulated by TGF-β and drives tumor progression. Conversely, CD73 is downregulated in endometrial carcinomas (EC) despite a TGF-β-rich environment. Through gene expression analyses of normal endometrium samples of the uterine cancer TCGA data set and genetic and pharmacological studies, we discovered CD73 loss shifts TGF-β1 from tumor suppressor to promoter in EC. TGF-β1 upregulated CD73 and epithelial integrity in vivo in the normal endometrium and in vitro in early stage EC cells. With loss of CD73, TGF-β1-mediated epithelial integrity was abrogated. EC cells developed TGF-β1-mediated stress fibers and macromolecule permeability, migration, and invasion increased. In human tumors, CD73 is downregulated in deeply invasive stage I EC. Consistent with shifting TGF-β1 activity, CD73 loss increased TGF-β1-mediated canonical signaling and upregulated cyclin D1 (CTNND1) and downregulated p21 expression. This shift was clinically relevant, as CD73(Low)/CCND1(High) expression associated with poor tumor differentiation, increased myometrial and lymphatic/vascular space invasion, and patient death. Further loss of CD73 in CD73(Low) expressing advanced stage EC cells increased TGF-β-mediated stress fibers, signaling, and invasiveness, whereby adenosine A1 receptor agonist, CPA, dampened TGF-β-mediated invasion. These data identify CD73 loss as essential for shifting TGF-β activity in EC.

Background This study aims to assess the association between body mass index (BMI) and health-related quality of life (HRQOL), and to further explore gender differences in BMI-HRQOL association among adults. Methods We used data from the fifth Health Service Survey of Shandong Province, which was part of China’s National Health Service Survey (NHSS), a total of 27,257 adults aged 18 and over were interviewed. The HRQOL was measured using the EuroQOL-5 Dimensions (EQ-5D) instrument. One-way ANOVA and Post hoc tests were used to compare EQ-5D utility values and visual analogue scale (VAS) scores between BMI categories. Tobit regression models were used to identify the association between BMI and HRQOL for male and female separately after controlling for influential confounders, and to assess gender differences on the relationship between BMI and HRQOL. Results The prevalence of underweight in men and women were 3.2 and 5.3%, respectively, while the prevalence of overweight/obesity in men and women were 35.7 and 34.6%, respectively. Men had higher EQ-5D utility values and VAS scores than women. The mean EQ-5D utility value and VAS score was highest in obese men and normal-weight women, respectively. After controlling potential confounders, being underweight was significantly and negatively associated with lower HRQOL among adults. The relationship between obesity and gender was that in women obesity was negatively and significantly associated with HRQOL, whereas in men this association was positive but not statistically significant. Results of gender by BMI interaction in regression model showed that this difference between men and women in this respect was significant. Conclusions The association between BMI and HRQOL differed by gender and the so-called “obesity-HRQOL paradox” phenomenon was verified in male adults. Gender difference should be considered when implementing targeted weight control programs and appropriate interventions to improve HRQOL.

This study aims to explore the association of anthropometric indices of obesity with hypertension in Chinese elderly and its possible gender and age differences. A total of 7070 adults age 60 or older were interviewed in a cross-sectional study conducted in 2017. Anthropometric indices for each participant were measured by using standard methods of trained doctoral/master students. We performed two binary logistic regression models to examine the association of the nine different anthropometric indices and hypertension by gender. Lastly, analyses were performed in two steps stratified for age. Comparing individuals with and without hypertension, there were statistically significant differences in anthropometric indices except height, a body shape index (ABSI), and hip index (HI) in males; and except height in females. There were gender differences in the relationship between anthropometric indices and the prevalence of hypertension in Chinese older adults. After stratification by age, the associations of all anthropometric indices became weaker, disappeared, or even went in the opposite direction. Furthermore, body mass index (BMI) in men (except individuals older than 80) and hip circumference (HC) in women showed a significant impact on the risk of hypertension. The association of anthropometric indices of obesity with hypertension in Chinese elderly differ by gender and age. These findings indicate a need to develop gender-specific strategies for the male and female elderly in the primary and secondary prevention of hypertension.

Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.

Assessment of estrogen receptor expression by immunohistochemistry has yielded inconsistent results as a prognostic indicator in ovarian carcinoma. In breast and endometrial carcinomas, panels of estrogen-induced genes have shown improved prognostic capability over the use of estrogen receptor immunohistochemistry alone. For both breast and endometrial cancer, over-expression of estrogen-induced genes is associated with better prognosis. We hypothesized that analysis of a panel of estrogen-induced genes can predict outcome in ovarian carcinoma and potentially differentiate between tumors of varying hormonal responsiveness. From a cohort of 219 women undergoing ovarian cancer surgery from 2004 −2007, 83 patients were selected for inclusion. All patients had advanced stage ovarian/primary peritoneal high-grade serous carcinoma and underwent primary surgical debulking followed by adjuvant treatment with platinum and taxane agents. The expression of ERα and six genes known to be induced by estrogen in the female reproductive tract (EIG121, sFRP1, sFRP4, RALDH2, PR, IGF-1) was measured using qRT-PCR. Unsupervised cluster analyses were used to categorize patients as high or low gene expressors. Gene expression results were then compared to those for estrogen receptor immunohistochemistry. Clusters were compared using chi-square analyses, and Cox proportional hazards were used to evaluate survival outcomes. Median follow-up time was 38.7 months (range 1–68). A cluster defined by EIG121 and ERα segregated tumors into distinct groups of high and low gene expressors. Shorter overall survival was associated with high gene expression (HR 2.84 [1.11–7.30], p=0.03), even after adjustment for other covariates. No difference in estrogen receptor immunohistochemistry expression was noted between gene clusters. In contrast to other hormonally-driven cancers, high expression of ERα and the estrogen-induced gene EIG121 predicts shorter overall survival in patients with high-grade serous ovarian carcinoma. Such a biomarker panel may potentially be used to guide management with estrogen antagonists in this patient population.

Follicular lymphomas (FLs) can be difficult to diagnose on aspirated specimens since the architectural pattern is not present. FLs characteristically have rearrangements in the IgH and BCL2 genes resulting from the reciprocal t(14;18) (q32; q21) translocation. Because of the dispersed distribution of breakpoints, fluorescence in situ hybridization (FISH) using genomic probes that span or flank the breakpoints is ideal for detecting this rearrangement in fine-needle aspiration (FNA) biopsies. To develop a set of probes, a bacterial artificial chromosome library was screened and the clones were mapped by fiber FISH. The probes were produced by the direct incorporation of fluorochrome-labeled nucleotides. The colocalization base FISH assay was applied to Cytospin preparations from FNA biopsies of lymph nodes from 26 patients with FL and 10 patients without FL. In those with FL, the percentage of cells with at least one IgH/BCL2 fusion signal ranged from 22% to 100% (mean, 63%), which was statistically significantly higher than that in FL-negative samples (mean, 2.7%). The probes demonstrated a significantly lower cutoff value (7%) in normal controls and effectively reduced the false-positive rate in FL-negative cases. These results were confirmed with fiber FISH assays on the same specimens. This interphase FISH assay is rapid and reliable for detecting rearrangements in the IGH/BCL2 gene, thereby aiding in the diagnosis of FL on FNA biopsy specimens.

In cultures, and in tissues as well, Hodgkin's and Reed-Sternberg (H-RS) cells and anaplastic large cell lymphoma (ALCL) cells are known to express a variety of cytokines, including IL-1, -5, -6, -8, -9, TNF-alpha, GM-CSF, M-CSF, TGF-beta, CD70, CD80, and CD86. Various numbers of H-RS/ALCL cells may express cytokine receptors (R), such as CD30, CD40, IL-2R (CD25/CD122), IL-6R (CD126), IL-7R (CD127), TNF-R (CD120), TGF-beta-R (CD 105/endoglin), M-CSF-R (CD115), and SCF-R (CD117/c-kit receptor). All of these cytokines and cytokine receptors are implicated in the growth regulation of H-RS/ALCL cells, the histopathologic alterations in tissues, and the clinical manifestations in patients with Hodgkin's disease (HD) or ALCL. Many of these cytokines or cytokine receptors also play an important role in the pathogenesis of other types of lymphomas. In this review, we describe the cytokine or cytokine-receptor expression that is diacritic for H-RS/ALCL cells. The identification of such unique cytokine-cytokine receptor interactions is likely to explain the biologic property that distinguishes HD/ALCL from other types of lymphomas. These interactions include those of CD30L-CD30, CD40L-CD40, CD70-CD27, CD80/CD86- CD28, SCF-CD117, IL-9-IL-9R, and IL-7-IL-7R. The H-RS/ALCL cells express IL-9 and two cytokine receptors, CD30 and CD117, which are observed infrequently in NHLs. Although IL-7 expression is not restricted to H-RS/ALCL cells, the expression of IL-7 in conjunction with IL-9 and/or CD117 may be regarded as unique for HD/ALCL because of an unusual combination and a synergistic activity among these cytokines. The expression of CD70 and CD80/CD86 (as cytokines) may exert a unique effect in HD because of intimate contact between H-RS cells and CD27/CD28-positive T cells. The expression of these costimulators (CD70 and CD80/CD86) and other adhesion/constimulator molecules such as CD54 and CD58, along with the secretion of soluble cytokines such as IL-1, IL-6, IL-7, or TNFs by H-RS/ALCL cells, could result in the profound T-cell proliferation often seen in lymph nodes involved by HD and some ALCL. On the other hand, the expression of CD30L and CD40L by surrounding T cells may affect the proliferation of H-RS/ALCL cells. The cytokine-cytokine receptor interaction between H-RS cells and T cells via direct cell-cell contact is bidirectional, a situation not commonly seen in NHLs. Copyright 1995 S. Karger AG, Basel

Polysomnography (PSG) is the standard method for obstructive sleep apnea hypopnea syndrome (OSAHS) diagnosis in medical, but the shortcomings in it have pushed many researchers to find a more convenient and effective way to detect OSAHS. With this purpose, a new technique for OSAHS assessment is proposed in this paper. It combined the properties of respiratory events with an ingenious dynamic threshold endpoint detection method to realize the automatic detection of respiratory events, and then obtained the apnea hypopnea index (AHI) to determine the patient's condition. The method was evaluated on the whole night snoring signal of 34 patients. Compared the results with those monitored by PSG, it has shown that the accuracy of this method can reach above 90%, at the same time, it has the advantages in low cost, high speed, easy to operate and so on.

The depressed cellular immunity observed in patients with Hodgkin's disease (HD) has been attributed to production of transforming growth factor (TGF)-beta or TGF-beta-like substances by Hodgkin's Reed-Sternberg (H-RS) cells. The TGF-beta produced by L-428 cells (an H-RS cell line) is a 130-kd molecular weight glycoprotein that apparently differs from the TGF-beta (molecular weight, 25 kd) produced by most lymphoid and hematopoietic cells. Among several distinct types of TGF-beta that have been purified, only TGF-beta 1 and TGF-beta 2 have thus far been identified in hematopoietic cells. By using monoclonal antibodies (1D11 and 3C7) and oligonucleotide probes specific for TGF-beta 1 and TGF-beta 2, were confirmed that a cultured H-RS cell line, KM-H2, can produce both TGF-beta types, whereas another line, HDLM-1, produces only TGF-beta 1. Despite the abundance of mRNA in both of these cells, only small amounts of TGF-beta activity were detected, probably because of rapid degradation of TGF-beta 1 mRNA by specific nuclease. No degraded TGF-beta 2 RNA products were observed in KM-H2 cells. The TGF-beta produced by both types of H-RS cells had a molecular weight of approximately 25 kd. In tissues expression of TGF-beta was observed in a small portion (30%) of H-RS cells in 16 of 20 cases examined. A large number of small to medium-sized lymphoid cells (T lymphocytes) in tissues involved by HD also were positive for TGF-beta. These results indicate that there is functional heterogeneity among H-RS cells, and that H-RS cells are not the only source of TGF-beta in tissues involved by HD. Hodgkin's Reed-Sternberg cells are known to secrete several other cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha. These cytokines could be responsible for the increased number of T lymphocytes in tissues involved by HD. Furthermore, T lymphocytes can respond to IL-1 and IL-6 secreted by H-RS cells by increasing their production of TGF-beta. Abundant expression of TGF-beta by T lymphocytes was not observed in lymphoid tissues other than those involved by HD.

The phenotypic expression of Russell bodies (RB) in the tumor cells of two patients with different types of B-cell lymphoma and of one patient with plasma cell myeloma were examined. In both B-cell lymphomas, the RBs reacted consistently with anti-Leu 8 and anti-immunoglobulin M. The RBs in one case also reacted with other monoclonal antibodies, including anti-CD5, CD19, CD22, and CD25. The membranes of most of the tumor cells containing RBs did not stain. In the myeloma, the RBs reacted only with anti-immunoglobulin, and the myeloma cells expressed no surface antigens associated with B lymphocytes. This finding suggests that RBs do not form in cells that can transport glycoproteins to the cell membrane, but rather occur as a result of defective transport or process of certain glycoproteins by plasmacytoid cells.

Objective: To study the clinicopathological characteristics of Lynch syndrome-associated endometrial carcinoma in China. Methods: Twenty-seven patients who fulfilled Amsterdam criteria II were classified as having Lynch syndrome-associated endometrial carcinoma (group A), and 331 patients without a family history of cancer were classified as having sporadic endometrial carcinoma (group B). Results: There were 81 malignancies in 27 families with Lynch syndrome-associated endometrial carcinoma, including colorectal cancer (24.7%), endometrial carcinoma (21.0%), and liver (12.3%), stomach (9.9%), lung (6.2%), and breast (6.2%) cancers. Mean age at the time of diagnosis was 49.7 years in group A and 56.3 years in group B (P = 0.004). Second primary cancers occurred in 33.3% of patients in group A and 5.1% in group B (P = 0.000). The most common second primary cancers were colorectal cancer (44%) and ovarian cancer (22%). The percentage of obese patients was higher in group A (P= 0.013). There was no difference between the 2 groups in incidence of diabetes mellitus or hypertension or in histological type and International Federation of Gynecology and Obstetrics stage. The 5-year survival rates for groups A and B were 96.2% and 79.6%, respectively. Prognosis for group A was better than for group B (P = 0.045). Conclusions: Some clinicopathological features of Lynch syndrome-associated endometrial carcinoma, such as early onset and multiple primary carcinomas are similar in the Chinese and American/European populations. However, the Chinese population had a unique family cancer distribution that included lung and breast cancers. Well-differentiated grade and good prognosis imply better biobehavior of Lynch syndrome-associated endometrial carcinoma in the Chinese population.

The true identity of Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells has been a subject of controversy for decades. Those who believe that Hodgkin's disease (HD) is a heterogeneous disease may consider it to constitute lymphomas of various origins. However, this theory seems incompatible with the finding of similar phenotypic, biologic, and immunologic properties among most HD. We believe that, in the majority of cases, HD, except for LP and some LD-type HD, is a homogeneous disease despite differences in the degree of fibrosis and/or cellular reaction. The heterogeneity in cellular reactions is a result of secretion of various cytokines by H-RS cells, which may or may not be influenced by the presence of EBV. H-RS cells, and anaplastic large cell lymphoma (ALCL) cells as well, can express a combination of cytokines and cytokine receptors that is not seen in other types of lymphomas. The unique cytokine/receptor profile (e.g. the expression of c-kit-R/CD117), along with various properties associated with H-RS/ALCL cells, leads to a hypothesis that H-RS/ALCL cells are related to similar lymphohematopoietic progenitor cells with different etiologies and somewhat limited differentiation capacity. A number of H-RS cells may differentiate with limited capacity along the B-cell pathway and may be infected by EBV, which further complicates the biologic and immunologic properties of these cells. The majority of H-RS cells may also, however, differentiate along the antigen-presenting dendritic cell pathway, as indicated by the abundant expression of restin, CD15, CD40, CD54, CD58, CD80, and CD86. The majority of ALCL cells clearly differentiate to T cells, but some may acquire B-cell or histiocyte phenotypes. The progenitor cell hypothesis may explain (1) the variable expression of CD117, CD43, and CD34 as well as the absence of CD27, CD45 and CD45RA in H-RS cells; (2) the inconsistent and irregular patterns of phenotype and genotype and the various, often very limited, degrees of differentiation among these two types of lymphoma cells; (3) the existence of secondary HD or ALCL associated with rare types of lymphomas or leukemias, or vice versa; (4) the absence of recombinase and of the B-specific transcription factors BSAP; and (5) the frequent expression of IL-7 and IL-9 in H-RS cells. Copyright 1996 S. Karger AG, Basel

Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas.