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The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies were obtained through appropriate databases and meetings abstracts search. A total of 29 studies were considered eligible for this review and it includes three Phase III studies, eighteen phase II studies and eight retrospective studies. For the Phase III studies, none have achieved an overall survival benefit; while for the Phase II studies, the majority have not achieved sufficient satisfactory outcome to justify advancement to Phase III studies. We believe that the best salvage treatment for MPM would be inclusion into appropriately designed clinical trials. In the absence of a clinical trial, gemcitabine and/or vinorelbine-based regimens could be considered. Moreover, pemetrexed re-challenge can be considered in selected pemetrexed-sensitive patients.

Non-visual arrestins (β-arrestins) are endocytic proteins that mediate agonist activated GPCRs internalization and signaling pathways in an independent manner. The involvement of β-arrestins in cancer invasion and metastasis is increasingly reported. So, it is hypothesized that inhibition of β-arrstins may diminish the survival chances of cancer cells. This study aimed to evaluate the in vitro impact of inhibiting β-arrestins on the autophagic and/or apoptotic responsiveness of breast cancer cells.We used Barbadin to selectively inhibit β-Arr/AP2 interaction in AVP stimulated V2R receptor of triple negative breast cancer cells (MDA MB-231). Autophagy was assessed by the microtubule-associated protein 1 light chain 3-II (LC3II), apoptosis was measured by Annexin-V/PI staining and cell cycle distribution was investigated based upon the DNA content using ow cytometry. Barbadin reduced cell viability to 69.1% and increased the autophagy marker LC3 II and its autophagic effect disappeared in cells transiently starved in Earle's balanced salt solution (EBSS). Also, Barbadin mildly enhanced the expression of P62 mRNA and arrested 63.7% of cells in G0/G1 phase. In parallel, the drug induced apoptosis in 29.9% of cells (by AV/PI) and 27.8% of cells were trapped in sub-G1 phase. The apoptotic effect of Barbadin was enhanced when autophagy was inhibited by the PI3K inhibitor (Wortmannin).Conclusively, the data demonstrate the dual autophagic and apoptotic effects of β-βArr/AP2 inhibition in triple negative breast cancer cells. These observations nominate β-Arrs as selective targets in breast cancer treatment.Thus, this work was designed to explore the autophagic and apoptosis effects of the inhibition of β-Arr/AP2 interaction in hormonally stimulated breast cancer cells. Materials And MethodsKey Reagents: Barbadin (3-amino-5-(4-benzylphenyl)-3H,4H-thieno[2,3-d]pyrimidin-4-one) (Cat No. B118250), Arginine Vasopressin acetic acid salt (AVP) (Cat No. V991535) and Wortmannin (Cat No. W499400), were purchased from Toronto Research Chemicals, Toronto, Ontario, Canada). Trichostatin A (TSA) and dimethyl sulfoxide (DMSO) were from Sigma Chemicals, USA. Earle's balanced salt solution (EBSS) and other cell culture reagents (DMEM 4.5 g/L glucose with L glutamine, penicillin/streptomycin, fetal bovine serum (FBS) and Trypsin/EDTA) were from Lonza Pharma & Biotech. Cell culture and treatment MDA MB-231 cells [16] was generously provided by Department of Cancer Biology, NCI, Cairo University.Cells were cultured in Dulbecco's modi ed Eagle's Minimal Essential Medium (DMEM) supplemented with 10% heat inactivated FBS, 1% Penicillin/Streptomycin in a humidi ed atmosphere of 95% air and 5% CO 2 at 37 °C. Initially, cells were seeded with a low cell density then subcultured with particular densities in 100 mm, 6 wells, or 96 wells plates according to the experimental settings. Cell treatmentsAutophagy was induced by glucose oxygen deprivation, where cells were starved for 4 hours in EBSS, which does not contain nutrients nor growth factors, at...

Background: PD-L1 expression differs from 19 to 92% in various cancer subtypes. Its expression carries a worse prognostic value in various malignancies and could also be used as a predictive marker for immune checkpoint inhibitor response. This study aimed to explore the prevalence of PD-L1 expression in soft tissue sarcomas and the correlation of PD-L1 expression with clinicopathological features.Patients and Methods: The tissue samples of 50 patients with STS were tested for PD-L1 expression using immunohistochemistry (IHC). We followed a 6-step proportional scoring system. The patients were treated at Ain Shams University Hospital from 2011 to 2017. We also explored the correlation of PD-L1 expression with different clinical features of the patients. The chi-square test was used to calculate the differences among variables.Results: Twelve cases (24%) showed positive PD-L1 expression with the highest prevalence in rhabdomyosarcoma and desmoid tumors (2/2 and 2/3 cases, respectively), followed by GIST in 2/4 cases and liposarcoma in 3/11 cases. Patients with positive PD-L1 expression showed a trend for worse survival, with a median overall survival of 11 months vs. 19 months for patients with negative PD-L1 expression (p-value = 0.1) and a mean PFS of 6 months vs. 11 months for patients with negative PD-L1 expression (p-value = 0.1). However, these findings did not reach statistical significance.Conclusion: Although the results did not reach statistical significance due to the small number of cases, PD-L1 expression could represent a prognostic factor for poor outcome. Larger clinical trials are recommended for the validation of PD-L1 as a poor prognostic biomarker.

PurposeBreast cancer is the most common cancer among females worldwide in general and in the Middle East and the North African region (MENA region) in particular. Management of breast cancer in the MENA region faces a lot of challenges, which include younger age at presentation, aggressive behaviour, lack of national breast screening programmes and lack of reliable data registries as well as socioeconomic factors. These factors make applying the international guidelines for breast cancer management very challenging. The aim of this project is to explore the need for a regional breast cancer guideline as well as to screen the clinical practice of breast cancer management in the MENA region.MethodologyThree web-based designed surveys were sent to more than 600 oncologists in the MENA region from the period of August 2013 to October 2014. Full descriptive data and information regarding the application of international breast cancer guidelines were collected. The software was using the IP address to prevent duplication of collected data. Descriptive analysis and results were shown as numbers and percentages.ResultsDuring the period of the survey, 104 oncologists responded, representing around an 11% response rate. The majority of replies came from Egypt (59 responses (59%)), followed by Saudi Arabia (ten responses (9.6%)). Fifty-one per cent of responders had more than ten years of experience, and further 31.7% had 5–10 years of experience. Seventy-four per cent were working in governmental hospitals, which is our target sector. There was a major defect in having a genetic counsel unit (78.8% declared an absence of this service), presence of a national breast screening programme (55.8% declared an absence of this service), performing sentinel lymph node biopsy (43.3% declared an absence of this service). The need for regional guidelines for the management of breast cancer was agreed upon by 90.6% of responders.ConclusionThere is a clear need to improve the management of breast cancer in the MENA region. Creating a national breast screening programme and a reliable database is essential. A regional guideline is required to establish the best possible management of breast cancer according to the patients and disease specification as well as the regional socioeconomic factors and facilities available. There is also a need to improve clinical research that meets the region’s needs.

The conventional methods used for the diagnostics of viral infection are either expensive and time-consuming or not accurate enough and dependent on consumable reagents. In the presence of pandemics, a fast and reagent-free solution is needed for mass screening. Recently, the diagnosis of viral infections using infrared spectroscopy has been reported as a fast and low-cost method. In this work a fast and low-cost solution for corona viral detection using infrared spectroscopy based on a compact micro-electro-mechanical systems (MEMS) device and artificial intelligence (AI) suitable for mass deployment is presented. Among the different variants of the corona virus that can infect people, 229E is used in this study due to its low pathogeny. The MEMS ATR-FTIR device employs a 6 reflections ZnSe crystal interface working in the spectral range of 2200-7000 cm-1. The virus was propagated and maintained in a medium for long enough time then cell supernatant was collected and centrifuged. The supernatant was then transferred and titrated using plaque titration assay. Positive virus samples were prepared with a concentration of 105 PFU/mL. Positive and negative control samples were applied on the crystal surface, dried using a heating lamp and the spectrum was captured. Principal component analysis and logistic regression were used as simple AI techniques. A sensitivity of about 90 % and a specificity of about 80 % were obtained demonstrating the potential detection of the virus based on the MEMS FTIR device.

Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. Methods Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. Results The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% ( p = 0.1) and median CD20 was 20% and 7.5% ( p = 0.008) in AR− and AR+, respectively. Mean CD3 was 80.7% and 93.3% ( p = 0.007) and CD8 was 75% and 80.8% ( p = 0.41) in AR− and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N− patients ( p = 0.03) with median TILs of 20% versus 50% in N+ versus N−, respectively ( p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05–34.21; p = 0.04). Conclusions AR expression was evident in older age (≥50 years). Median CD20 was higher in AR− TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

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