MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.     

Burkholderia pseudomallei in Environment of Adolescent Siblings with Melioidosis,Kerala, India, 2019

In 2019, Burkholderia pseudomallei was isolated from the backyard of 2 siblings with melioidosis in Kerala, India. This finding highlights the value of healthcare providers being aware of risk for melioidosis in febrile patients, of residents taking precautions when outside, and of increasing environmental surveillance for B. pseudomallei in this region.     

In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Nanomagnet-facilitated pharmaco-compatibility for cancer diagnostics: Underlying risks and the emergence of ultrasmall nanomagnets

Cancer therapy is a fast-emerging biomedical paradigm that elevates the diagnostic and therapeutic potential of a nanovector for identification, monitoring, targeting, and post-treatment response analysis. Nanovectors of superparamagnetic iron oxide nanoparticles (SPION) are of tremendous significance in cancer therapy because of their inherited high surface area, high reactivity, biocompatibility, superior contrast, and magnetic and photo-inducibility properties. In addition to a brief introduction, we summarize various progressive aspects of nanomagnets pertaining to their production with an emphasis on sustainable biomimetic approaches. Post-synthesis particulate and surface alterations in terms of pharmaco-affinity, liquid accessibility, and biocompatibility to facilitate cancer therapy are highlighted. SPION parameters including particle contrast, core-fusions, surface area, reactivity, photosensitivity, photodynamics, and photothermal properties, which facilitate diverse cancer diagnostics, are discussed. We also elaborate on the concept of magnetism to selectively focus chemotherapeutics on tumors, cell sorting, purification of bioentities, and elimination of toxins. Finally, while addressing the toxicity of nanomaterials, the advent of ultrasmall nanomagnets as a healthier alternative with superior properties and compatible cellular interactions is reviewed. In summary, these discussions spotlight the versatility and integration of multi-tasking nanomagnets and ultrasmall nanomagnets for diverse cancer theragnostics.     

Effect of intravenous immune globulin on natural killer cell activity: possible association with autoimmune neutropenia and idiopathic thrombocytopenia

Natural killer cell (NK) activity was assessed in patients before and after treatment with intravenously administered immune globulin (IVIG). In eight patients with hypogammaglobulinemia or agammaglobulinemia receiving 300 mg/kg/dose IVIG every 4 weeks, NK activity was significantly lower after therapy than before. In two patients, one with idiopathic thrombocytopenic purpura and one with autoimmune neutropenia, receiving high doses (2 gm/kg) of IVIG, NK activity was unusually high before therapy. After treatment, NK activity decreased in correlation with the clinical response and elevation of peripheral cell counts. These data show that IVIG diminishes NK activity in vivo and that reduction of NK activity may be associated with clinical improvement in idiopathic thrombocytopenic purpura and autoimmune neutropenia. NK activity of lymphocytes obtained from healthy volunteers was reduced by the same concentrations of maltose or sucrose present in Gamimune or Sandoglobulin, respectively; IVIG preparations, however, were more inhibitory. The diminution of NK activity therefore may be related to two components of IVIG preparations, monomeric IgG and maltose or sucrose.     

Timely follow‐up of positive cancer screening results: A systematic review and recommendations from the PROSPR Consortium

Timely follow‐up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow‐up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer‐specific recommendations for times to follow‐up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow‐up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow‐up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low‐resource settings. CA Cancer J Clin 2018;68:199–216 . © 2018 American Cancer Society .     

Supracervical hysterectomy in patients with advanced epithelial ovarian cancer

OBJECTIVE: To assess whether supracervical hysterectomy (SCH) is a reasonable alternative to total abdominal hysterectomy in patients with advanced ovarian cancer. METHODS: We reviewed the records of patients with advanced ovarian cancer who underwent a SCH at one institution between 1993 and 2004 and a similar cohort who underwent total abdominal hysterectomy (TAH) at the same institution during the same period. Patients without complete surgical staging done at the institution were excluded. Independent-sample t tests, Fisher exact test, and log rank tests were used for statistical analysis. RESULTS: The study included 47 patients who underwent SCH (mean age, 59.6 years) and 190 who underwent TAH. There were no significant differences between the two groups in age (P=.51), preoperative CA 125 level (P=.55), or receipt of taxane-based and platinum-based chemotherapy (P=.84). Although limited by sample size, there were no significant differences between the two groups in rates of intraoperative complications (4 of 47 in the SCH group, or 8.5%, compared with 7 of 190 in the TAH group, or 3.7%; P=.24), vaginal or cervical recurrence (5 of 47 in the SCH group, or 10.6%, compared with 22 of 190 in the TAH group, or 11.6%; P=1.00), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12). CONCLUSION: Supracervical hysterectomy may be a reasonable alternative to TAH in patients with advanced ovarian cancer. LEVEL OF EVIDENCE: II.     

Open ring enhancement in atypical brain demyelination

Open ring enhancement is considered highly specific for atypical demyelination. In this report we present a patient with a history of headache, ataxia and sensory disturbances in the lower extremities. A cranial MRI scan showed a large frontal lesion with mass effect, midline shift and with open ring enhancement. These findings are characteristics of tumefactive multiple sclerosis. Such lesions can be confused with neoplasms and abscesses. Open ring enhancement may help in differentiating atypical demyelination from a neoplasm or an abscess.