Blalockburke1347

PURPOSE HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients. METHODS Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors. RESULTS Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence. CONCLUSIONS High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.BACKGROUND AND AIMS Compared to the general population, the incidence of thyroid cancer in childhood and adolescent and young adult malignancy survivors is increased 14.0-18.0 times (CI 11.7-23.8). The cumulative incidence is variably reported as 0.5% by age 45 with 30-year incidence of 1.3% in women and 0.6% in men. This study aims to evaluate the incidence of radiation-associated thyroid cancer amongst patients treated with prior radiation to the thyroid followed up in a late effects service. A secondary aim was to assess screening compliance in this cohort. METHODS The medical records of all patients attending the late effects service from 1 January 2000 to 20 February 2013 were interrogated to identify patients exposed to thyroid irradiation. The screening compliance and incidence of thyroid cancer were assessed for the duration whilst under the guidance of the late effect service. Mode of diagnosis, all imaging and cytology were retrieved from the institutional electronic record. Cytology was categorizedfine-needle aspiration cytology based on sonographic criteria as for the general population and American Thyroid Association guidelines.BACKGROUND This study aimed to highlight cultural barriers faced by surgeons pursuing a surgical career faced by surgeons at a tertiary care hospital in Pakistan. As more females opt for a surgical career, barriers faced by female surgeons are becoming increasingly evident, many of which are rooted in cultural norms. In Pakistan, a predominantly Muslim-majority, low middle-income country, certain societal expectations add additionally complexity and challenges to existing cultural barriers. METHODS A cross-sectional survey was administered via e-mail to the full-time faculty and trainees in the Department of Surgery at the Aga Khan University Hospital, Karachi, Pakistan, from July 2019 to November 2019. RESULTS In total, 100 participants were included in this study, with the majority being residents (55.6%) and consultants (33.3%). 71.9% of female surgeons felt that cultural barriers towards a surgical career existed for their gender, as compared to 25.4% of male surgeons (p  less then  0.001). 40.6% of females reported having been discouraged by family/close friends from pursuing surgery, as compared to only 9.0% of males (p  less then  0.001). Moreover, a greater percentage of females surgeons were responsible for household cooking, cleaning and laundry, as compared to male surgeons (all p  less then  0.001). Lastly, 71.4% of female surgeons felt that having children had hindered their surgical career, as compared to 4.8% of males (p  less then  0001). CONCLUSION Our study shows that significant cultural barriers exist for females pursuing a surgical career in our setting. Findings such as these emphasize the need for policy makers to work towards overcoming cultural barriers.INTRODUCTION For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab. MATERIALS AND METHODS Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status. RESULTS Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples. CONCLUSIONS Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.Women in reproductive age with rheumatic diseases (RD) are especially vulnerable for depression and anxiety which negatively impacts the pregnancy, birth, and RD. The purpose of this study is to describe the frequency of anxiety and depression symptoms employing the Hospital Anxiety and Depression Scale (HADS) in women in reproductive age. We conducted an observational, single-center, cross-sectional, and descriptive study in reproductive-age, non-pregnant women without a prior psychiatric diagnosis. Differences between disease groups, subscale results, and disease activity were analyzed with the Chi square, Mann-Whitney U test, or Kruskal-Wallis test. A total of 100 women were included. Mean age was 35.3 years (SD = 10.07). The most frequent diagnosis was rheumatoid arthritis (RA) with 48, followed by systemic lupus erythematosus (SLE) with 30. A total of 66 (66%) patients had an abnormal HADS score (probable or possible cases) in either subscale. More than 50% of RA patients had an abnormal HADS score. We found an association between RA disease activity groups and total HADS score (p = 0.003). Furthermore, we found a statically significant association between RA activity groups and HADS anxiety subscales group classification (p = 0.01). No differences between disease activity groups of SLE or other diseases and HADS classification or total score was found (p = 0.277). A high frequency of probable or possible cases of depression and anxiety were recognized in reproductive-age women with RD. A high RA disease activity was associated with a high total HADS score and an increased presence of anxiety symptoms.Increased proteolytic activity of cysteine cathepsins has long been known to facilitate malignant progression, and it has also been associated with tumor-promoting roles of myeloid-derived suppressor cells (MDSCs). Consequently, cysteine cathepsins have gained much attention as potential targets for cancer therapies. However, cross-talk between tumor cells and MDSCs needs to be taken into account when studying the efficacy of cathepsin inhibitors as anti-cancer agents. Here, we demonstrate the potential of the MDA-MB-231 breast cancer cell line to generate functional MDSCs from CD14+ cells of healthy human donors. During this transition to MDSCs, the overall levels of cysteine cathepsins increased, with the largest responses for cathepsins L and X. We used small-molecule inhibitors of cathepsins L and X (i.e., CLIK-148, Z9, respectively) to investigate their functional impact on tumor cells and immune cells in this co-culture system. Interactions with peripheral blood mononuclear cells reduced MDA-MB-231 cell invasion, while inhibition of cathepsin X activity by Z9 restored invasion. Inhibition of cathepsin L activity using CLIK-148 resulted in significantly increased CD8+ cytotoxicity. Of note, inhibition of cathepsins L and X in separate immune or tumor cells did not promote these functional changes. Together, our findings underlie the importance of tumor cell-immune cell interactions in the evaluation of the anti-cancer potential of cysteine cathepsin inhibitors.BACKGROUND Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. find more This study aims to explore the role of immune-related genes in the development of LUAD and establish a signature that can predict overall survival for LUAD patients. METHODS To identify the differential expression genes (DEGs) between normal and tumor tissues, we developed an analysis strategy to combine an independent-sample design and a paired-sample design using RNA-seq transcriptomic profiling data of The Cancer Genome Atlas LUAD samples. Further, we selected prognostic markers from DEGs and evaluated their prognostic value in a prediction model. RESULTS We identified and validated PD1, PDL1 and CTLA4 genes as prognostic markers, which are well-known immune checkpoints, and revealed two new potential prognostic immune checkpoints for LUAD, HHLA2 (logFC = 2.55, FDR = 1.89 × 10-6) and VTCN1 (logFC = -2.86, FDR = 1.72 × 10-11). Furthermore, we identified an 18-gene LUAD prognostic biomarker panel and observed that the classified high-risk group presented a significantly shorter overall survival time (HR = 3.57, p value = 4.07 × 10-10). The prediction model was validated in five independent high-throughput gene expression datasets. CONCLUSIONS The identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis.BACKGROUND Plantago lanceolata L. is used in Iraqi folklore medicine to treat injuries, and its extract is prescribed by some herbalists for cancer patients. This research aimed to evaluate the effect of P. lanceolata leaf extract on breast cancer cell lines in vitro and to identify its active compounds. Crystal violet viability assay was used to determine the cytotoxicity of methanolic P. lanceolata leaf extract against various breast cancer cell lines. MCF7, AMJ13, MDAMB, and CAL51 human breast cancer cells were treated with different concentrations of the extract for 72 h. The morphology of the treated cells was examined under a phase-contrast inverted microscope. The clonogenic ability was assessed through a clonogenic assay. High-performance liquid chromatography (HPLC) analysis was performed to measure the concentrations of phenols and flavonoids in the extract. RESULTS The methanolic P. lanceolata leaf extract significantly inhibited the proliferation of triple-negative CAL51 cells but showed minor effect on the other breast cancer cells.