The metabolic cross‐talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Cancer and stromal cells, which include (cancer‐associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem‐like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer‐associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro‐inflammatory cytokines and the release of autophagy‐derived metabolites and substrates. Interrupting the metabolic cross‐talk between cancer cells and cancer‐associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.     

Prevalence and risk factors for gastroschisis in a public hospital from west México

Mexico is recognized as a country with a high prevalence of gastroschisis, although the cause of this remains unclear. We define the prevalence and potential risk factors for gastroschisis in a public hospital from west México. A case‐control study was conducted among 270 newborns, including 90 patients with nonsyndromic gastroschisis (cases) and 180 infants without birth defects (controls), born all during the period 2009 to 2013 at the Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” (Guadalajara, Mexico), from a total of 51 145 live births. Potential maternal risk factors for gastroschisis were compared using multivariate logistic regression analysis to evaluate the deviance explained by different variables of interest. The overall prevalence of gastroschisis in live births was 17.6 per 10 000 births (95% confidence interval [CI] 14.0–21.2), whereas in offspring of women ≤19 years old was 29.9 per 10 000 births (95% CI 21.9–38.0). Mothers ≤19 years (adjusted odds ratio [aOR] 2.8: 95% CI 1.5–5.1), anemia during pregnancy (aOR 10.7; 95% CI 2.0–56.9), first‐trimester exposure to hormonal contraceptives (aOR 3.7; 95% CI 1.0–13.0), and first‐trimester alcohol consumption (aOR 3.4; 95% CI 1.6–7.3), were associated with gastroschisis. Contrarily, adjusted OR for pre‐pregnancy body mass index ≥25 kg/m² has protective odds (aOR 0.2; 95% CI 0.1–0.5). Our results suggest an increased risk for gastroschisis among mothers under the age of 20, with anemia during pregnancy, and those who used hormonal contraceptives or consumed alcohol during early pregnancy, whereas, pre‐pregnancy overweight has a protective OR, and they are discussed as clues in its pathogenesis.     

Selective depression of interferon-gamma and granulysin production with increase of proliferative response by Vgamma9/Vdelta2 T cells in children with tuberculosis

Vgamma9/Vdelta2 T cells can contribute to protective immune response against Mycobacterium tuberculosis, although the extent to which and mechanisms by which they could actually protect against human tuberculosis remain unclear. We have previously reported that Vgamma9/Vdelta2 T cells from tuberculin purified protein derivative (PPD)-positive children, either healthy or affected by different clinical forms of tuberculosis, strongly proliferate to different phosphoantigens in vitro, whereas Vgamma9/Vdelta2 T cells from PPD-negative healthy subjects proliferate very poorly. We report here that Vgamma9/Vdelta2 T cells from tuberculous children have an increased proliferative activity, but decreased interferon (IFN)-gamma production and granulysin expression. After successful chemotherapy, the Vgamma9/Vdelta2 T cell proliferative response strongly decreased, whereas IFN-gamma and granulysin production consistently increased. Disease-associated changes in Vgamma9/Vdelta2 T cell effector functions in patients with tuberculosis are consistent with the possibility that these T cells may play a protective role in immune response against M. tuberculosis infection.     

IGFBP-3 Mediates Metabolic Homeostasis During Hyperosmolar Stress in the Corneal Epithelium

PurposeThe insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional secretory protein with well-known roles in cell growth and survival. Data in our laboratory suggest that IGFBP-3 may be functioning as a stress response protein in the corneal epithelium. The purpose of this study is to determine the role of IGFBP-3 in mediating the corneal epithelial cell stress response to hyperosmolarity, a well-known pathophysiological event in the development of dry eye disease.MethodsTelomerase-immortalized human corneal epithelial (hTCEpi) cells were used in this study. Cells were cultured in serum-free media with (growth) or without (basal) supplements. Hyperosmolarity was achieved by increasing salt concentrations to 450 and 500 mOsM. Metabolic and mitochondrial changes were assessed using Seahorse metabolic flux analysis and assays for mitochondrial calcium, polarization and mtDNA. Levels of IGFBP-3 and inflammatory mediators were quantified using ELISA. Cytotoxicity was evaluated using a lactate dehydrogenase assay. In select experiments, cells were cotreated with 500 ng/mL recombinant human (rh)IGFBP-3.ResultsHyperosmolar stress altered metabolic activity, shifting cells towards a respiratory phenotype. Hyperosmolar stress further altered mitochondrial calcium levels, depolarized mitochondria, decreased levels of ATP, mtDNA, and expression of IGFBP-3. In contrast, hyperosmolar stress increased production of the proinflammatory cytokines IL-6 and IL-8. Supplementation with rhIGFBP-3 abrogated metabolic and mitochondrial changes with only marginal effects on IL-8.ConclusionsThese findings indicate that IGFBP-3 is a critical protein involved in hyperosmolar stress responses in the corneal epithelium. These data further support a new role for IGFBP-3 in the control of cellular metabolism.     

Parental occupation and neural tube defect-affected pregnancies among Mexican Americans

In a case-control study, we examined whether parental occupational exposures were related to neural tube defect (NTD)-affected pregnancies among Mexican Americans living along the Texas-Mexico border. Case women were 184 Mexican-American women with NTD-affected pregnancies; control women were 225 study-area residents who delivered normal babies during the same period as the case women. The women were interviewed in person about maternal and paternal occupations and work exposures during the periconceptional period. Compared with control women, case women were more likely to have had occupational exposures to solvents (odds ratio [OR], infinity; 95% confidence interval [CI], 2.4-infinity) and also were more likely to have worked in cleaning (OR 9.5; 95% CI, 1.1 to 82.2) or health care occupations (OR 3.0; 95% CI, 1.0 to 9.0) than control women. No compelling associations were found between paternal work exposures or occupations and NTDs in offspring in this population.     

Splenic vein thrombosis: an unusual case of gastric bleeding.

Acute and/or recurrent gastrointestinal bleeding due to ruptured gastric varices from an isolated thrombosed splenic vein is a distinct entity. Incidence of this syndrome is probably less than 1%. Typical clinical features of this syndrome include evidence of splenic hypertension without liver disease and no demonstrable cause of gastrointestinal hemorrhage. Diagnosis can easily be missed unless the surgeon is familiar with this syndrome. Typical findings at the time of surgery are an enlarged spleen, varicose veins usually involving the upper third of the stomach, and pancreatic and peripancreatic inflammation. Portal vein and portal pressure will be normal. Meso-portography is a convenient and safe procedure and will lend support to suspicion when a retrograde nonfilling of the splenic vein is present. Splenectomy offers the expectation of a long-range cure. A representative case of a 39-year-old man is discussed. He had at least six episodes of gastric bleeding in less than 3 years. At a previous laparotomy, the cause of bleeding could not be determined. A splenectomy in December 1970 has been able to control the gastric bleeding since then.