Nowadays combination of various therapeutic modalities is an attractive strategy in cancer treatment. In order to develop more efficient combinational therapy, we investigated the effect of Vitamin K3 (menadione) to enhance the cytotoxic action of chemo-photodynamic therapy against Rhabdomyosarcoma (RD) cell line, using Photosense as a photosensitizer and different chemo therapeutic agents. RD cell line was cultured for the evaluation of efficacy in the presence and absence of vitamin K3 with other chemotherapeutic agents. Diode laser (λ = 635 nm) was used for initializing the photodynamic action of Photosense mediated photodynamic therapy (PDT). Cytotoxicity was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pre-treatment for 24 h to RD cells with K3 significantly potentiates sensitivity of chemotherapy. Chemotherapeutic agents and K3 showed significant killing effect when combined with PDT, at very low doses. These results suggest that this procedure could be the basis for an improved chemo-PDT protocol for cancer control.
Objective: The aim of this study is to determine the effectiveness of tranexamic acid for seroma prevention in obese patients undergoing laparoscopic ventral hernia repair under spinal anesthesia. Study Design: Cross sectional study Place and Duration: Jinnah Postgraduate Medical Center (JPMC) Karachi, 1st July 2020 to 30th June 2021. Methods: There were one hundred and ten patients f both genders had abdominal hernia were included in this study. We have taken written consent from all the patients for detailed demographics age, sex and body mass index. Patients were undergone for laparoscopic ventral hernia repair under spinal anesthesia in OPD. The size and contents of the defect were determined by an abdominal and pelvic ultrasound. All patients received postoperative tranexamic acid. Drains were put in to measure the amount of seroma that was produced as a result of the procedure. SPSS 22.0 was used to analyze all of the data. Results: 42.23±6.55 years were the mean age of the patients. Mean Body mass index was 32.13±3.43 kg/m2. Majority of the patients 74 (67.3%) were females and rest of the patients 36 (32.7%) were males. In 91 (82.7%) cases seroma reduction was calculated within week. Only 41 of the 110 patients had drain output of less than 150 ml, 55 had drain output of 150-300 ml, and 14 had drain output greater than 300 ml. Seroma formation was found among 7 (6.4%) cases. Conclusion: Tranexamic acid was found to be efficient in minimizing postoperative seroma formation in ventral hernia repairs, according to the findings of this study. Keywords: Laparoscopic, Tranexamic acid, Plasminogen, Seroma, Obese Patients
Objective: The aim of this study is to compare the ICU stay and mortality in vaccinated and non-vaccinated covid-19 patients. Study Design: A Retrospective/ Comparative study Place and Duration: The study was conducted in Medicine department of Fauji Foundation Hospital Rawalpindi, duration of six months from October 2020 to March 2021. Methods: Total 120 patients of both genders had coronavirus disease were presented in this study. Patients were aged between 22-80 years. Demographical details of patients including age, sex, body mass index, residency and socio-economic status were recorded after taking informed written consent. Patients were admitted in COVID 19 ward. Chest X-rays of both groups were taken. There were 50 vaccinated patients in group I and 70 non-vaccinated patients in group II. Co-morbidities among both groups were assessed. Recovery and outcomes among both groups were calculated in terms of mortality and reduction in severity of disease. Complete data was analyzed by SPSS 24.0 version. Results: There were 80 (66.7%) patients were males (35 in group I and 45 in group II) and 40 (33.3%) were females (15 in group I and 25 in group II). Mean age of the vaccinated patients was 46.21 ±9.67 years with mean BMI 32.12 ±6.33 kg/m2 and in group II mean age was 45.13 ±21.54 years with mean BMI 33.11±11.37 kg/m2. 34 (68%) were educated in group I and in group II 35 (50%) patients were literate. Severity of disease among non-vaccinated patients was high found in 55 (78.6%) cases as compared to vaccinated cases 17 (34%). Co-morbidities were diabetes mellitus, hypertension, ischaemic heart and chronic lung disease. Most of the patients 90 (75%) had bilateral lung involvement and interstitial infiltrates 105 (87.5%). Fever, cough and dyspnea were the most common symptom found in both groups. Recovery among patients of group I was greater 40 (80%) as compared to non-vaccinated 27 (38.6%). Frequency of poor outcomes hospitalization 9 (12.9%), ICU admission 11 (15.8%) and mortality 23 (32.9%) among non-vaccinated patients were significantly higher as compared to vaccinated patients in which hospitalization 2 (4%), ICU admission 3 (6%) and mortality was found in 5 (10%) cases. Conclusion: According to the findings of this study, vaccination against coronavirus disease is both efficacious and beneficial in reducing disease severity. Except for this, immunization can reduce the frequency of poor outcomes (hospitalization, ICU admission, and mortality), and individuals should be made aware of the importance of becoming vaccinated as soon as possible. Keywords: COVID 19, Vaccination, Pandemic, Mortality
Immunotherapy has shown limited success in pancreatic adenocarcinoma (PDAC) patients. To improve clinical management of cancer, it is crucial to identify alternative immunostimulatory targets associated with mechanisms of tumor evolution to facilitate the development of novel combination immunotherapies. Here we categorized PDACs and other cancers (n>7,500) into subgroups based on immunostimulatory glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related ligand (GITRL) and receptor (GITR) expression: GITRLhigh+GITRhigh and GITRLhigh/low+GITRlow. We characterized immune evasion mechanisms using immunotherapy preclinical trials in four representative immunocompetent mouse models, finding that the GITR agonist, DTA-1 significantly improved responses in GITRLhigh(+GITRhigh) tumors (n=2). Further characterization revealed increased activation of CD8+ T-cells (but not T-regulatory; Tregs cells) and enhanced interferon-γ, immunoproteosome, antigen presentation, and T-cell receptor (TCR) gene expression in DTA-1 responders. In vivo clonal tracking using DNA barcoding showed that GITR agonist therapy significantly reduced tumor burden by targeting expansion of heterogeneous PDAC clones and not clone-initiating cells (representing potential resistance). However, emerging GITRLhigh+GITRhigh epithelial-like oligoclones from the responder model escaped immune surveillance to GITR agonist treatment via increased PD-L1, offering a combined anti-PD-L1, CD40 agonist and DTA-1 immunotherapy regimens (with/without chemotherapy) that further improved responses by decreasing PD-L1+ myeloid cells. Conversely, mesenchymal-enriched GITRLlow models exhibited primary (intrinsic) resistance to GITR agonist treatment due to reduced T-cells and increased myeloid and/or PD-L1+ non-immune cells. These results provide pre-clinical context for GITR+PD-L1+CD40-based personalized immuno-chemotherapy combinations for PDAC.
The combination of therapeutic drugs interestingly enhances treatment outcomes compared to single-agent modalities. Vitamin D3 (VD) in the presence of photodynamic drugs likewise affects the therapeutic results. A rhabdomyosarcoma (RD) cell line was cultured for the evaluation of each therapeutic agent, i.e. photodynamic therapy (PDT), chemotherapy (Chemo), and their combination with and without VD. Diode laser (λ = 630 nm ± 1 nm) was used as an illumination source. The uptake time of the photosensitizer was optimized by means of spectrophotometric measurements. Administered drug responses were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. VD treatment for 24 h enhanced cellular death by 10%–30% when used as a neoadjuvant agent in chemotherapy (cisplatin (CDDP), doxorubicin (DOX), and methotrexate (MTX)), thereby exhibiting synergistic effects (CI < 1). RD culture pretreated with VD for 24 h showed encouraging results (% viability) when exposed to CDDP (~50%), DOX (~50%), and MTX (~58%). Culture after treatment with VD + Chemo (CDDP, DOX, MTX) was followed by PDT, and more encouraging therapeutic outcomes (~80%, ~70%, and ~76%, respectively) were observed compared to prior treatment evaluation. VD-Chemo or VD-chemo-PDT therapeutic modalities based on prior measured optimal parameters showed good anti-cancer effects. These results suggest that the proposed sequence of combinational therapeutic agents may further enhance the existing cancer-treatment protocol.
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