Omarhong8597
naLAT1/3T3 had stronger growth- and malignancy- related phenotypes than NIH/3T3 and muLAT1/3T3, suggesting the oncogenicity of native LAT1 through its interaction with CD98hc. Anti-LAT1 monoclonal antibodies significantly inhibited in vitro cell proliferation and in vivo tumor growth of naLAT1/3T3 cells in nude mice, demonstrating LAT1 to be a promising anti-cancer target.
Resistance to antiproliferative chemotherapies remains a significant challenge in the care of patients with solid tumors. Glucocorticoids, including endogenous cortisol, have been shown to induce pro-survival pathways in epithelial tumor cells. While pro-apoptotic effects of glucocorticoid receptor (GR) antagonism have been demonstrated under select conditions, the breadth and nature of these effects have not been fully established.
To guide studies in cancer patients, relacorilant, an investigational selective GR modulator (SGRM) that antagonizes cortisol activity, was assessed in various tumor types, with multiple cytotoxic combination partners, and in the presence of physiological cortisol concentrations.
In the MIA PaCa-2 cell line, paclitaxel-driven apoptosis was blunted by cortisol and restored by relacorilant. In the OVCAR5 cell line, relacorilant improved the efficacy of paclitaxel and the potency of platinum agents. A screen to identify optimal combination partners for relacorilant showed that microtubule-targeted agents consistently benefited from combination with relacorilant. These findings were confirmed in xenograft models, including MIA PaCa-2, HeLa, and a cholangiocarcinoma patient-derived xenograft.
, tumor-cell apoptosis was increased when relacorilant was added to paclitaxel in multiple models.
These observations support recently reported findings of clinical benefit when relacorilant is added to paclitaxel-containing therapy in patients with ovarian and pancreatic cancers and provide a new rationale for combining relacorilant with additional cytotoxic agents.
These observations support recently reported findings of clinical benefit when relacorilant is added to paclitaxel-containing therapy in patients with ovarian and pancreatic cancers and provide a new rationale for combining relacorilant with additional cytotoxic agents.Breast cancer (BC) in Nigeria is characterized by disproportionately aggressive molecular subtypes. C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer. We examined the association of high-sensitivity CRP (hsCRP) with odds of BC by molecular subtype among Nigerian women. Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between hsCRP and odds of BC overall and by molecular subtype (luminal A, luminal B, HER2-enriched and triple-negative or TNBC). High hsCRP (> 3 mg/L) was observed in 57% of cases and 31% of controls and was associated with 4 times the odds of BC (aOR 4.43; 95% CI 2.56, 7.66) after adjusting for socio-demographic, reproductive, and clinical variables. This association persisted regardless of menopausal status and body mass index (BMI) category. High hsCRP was associated with increased odds of TNBC (aOR 3.32; 95% CI 1.07, 10.35), luminal A BC (aOR 4.03; 95% CI 1.29, 12.64), and HER2-enriched BC (aOR 6.27; 95% CI 1.69, 23.25). Future studies are necessary in this population to further evaluate a potential role for CRP as a predictive biomarker for BC.Despite the rising incidence of human papillomavirus related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), treatment of metastatic disease remains palliative. Even with new treatments such as immunotherapy, response rates are low and can be delayed, while even mild tumor progression in the face of an ineffective therapy can lead to rapid death. Real-time biomarkers of response to therapy could improve outcomes by guiding early change of therapy in the metastatic setting. Herein, we developed and analytically validated a new droplet digital PCR (ddPCR)-based assay for HPV16 circulating tumor DNA (ctDNA) and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV+ OPSCC. We found that longitudinal changes HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging (average 70 days, range 35-166). With additional validation in multi-site studies, this assay may enable early identification of treatment failure, allowing patients to be directed promptly toward clinical trials or alternative therapies.Surgical resection of head and neck squamous-cell carcinoma (HNSCC) is associated with high rates of local and distant recurrence, partially mitigated by adjuvant therapy. A pre-existing immune response in the patient's tumor is associated with better outcomes following treatment with conventional therapies, but improved options are needed for patients with poor anti-tumor immunity. We hypothesized that local delivery of tumor antigen-specific T-cells into the resection cavity following surgery would direct T-cells to residual antigens in the margins and draining lymphatics and present a platform for T-cell-targeted immunotherapy. We loaded T-cells into a biomaterial that conformed to the resection cavity and demonstrated that it could release T-cells that retained their functional activity in-vitro, and in a HNSCC model in-vivo. Locally delivered T-cells loaded in a biomaterial were equivalent in control of established tumors to intravenous adoptive T-cell transfer, and resulted in the systemic circulation of tumor antigen-specific T-cells as well as local accumulation in the tumor. We demonstrate that adjuvant therapy with anti-PD1 following surgical resection was ineffective unless combined with local delivery of T-cells. These data demonstrate that local delivery of tumor-specific T-cells is an efficient option to convert tumors that are unresponsive to checkpoint inhibitors to permit tumor cures.
The benefits of laparoscopic approach for right colectomy have been well established. However, the technical difficulty to construct the intra-corporeal anastomosis is still cumbersome.
To analyze the results of 3D and 2D laparoscopic right colectomy and to compare it to the published series through a systematic review and meta-analysis.
A retrospective study with propensity score matching analysis of patients undergoing laparoscopic right colectomy at Umbria2 Hospitals from January 2014 to March 2020 was performed. A systematic review was accomplished comparing 2D and 3D right colectomy.
In the personal series 47 patients of the 2D group were matched to 47 patients of the 3D group. The 3D group showed a favorable trend in terms of mean operative time (170.7 ± 32.9 min
183.8 ± 35.4 min;
= 0.053) and a significant lower anastomotic time (16.9 ± 2.3 min
19.6 ± 2.9 min,
< 0.001). The complete mesocolic excision (CME) subgroups analysis showed a shorter anastomotic time (16.5 ± 1.8 min
1oscopic right colectomy shortens operative and anastomotic time without affecting the standard lymphadenectomy. In our series, the advantage of the 3D system becomes evident when CME and/or more complex associated procedure are requested significantly reducing both the total operative and the anastomotic time.
Chylous ascites is a rare complication in colorectal surgery with limited evidence.
To systematically review all available evidence to describe the incidence, clinical presentation, risk factors and management strategies.
The systematic review was performed through PubMed, MEDLINE, EMBASE and Cochrane and cross-checked up to November 2020. The data collated included Demographics, indications (benign
malignant), site of disease, surgical approach, extent of lymphadenectomy, day to and method of diagnosis of chylous ascites and management strategies.
A total of 28 studies were included in the final analysis (426 cases). Patient age ranged from 31 to 89 years. All except one case were performed for malignancy. Of the 426 cases, 195 were right-colonic, 121 left-colonic, 103 pelvic surgeries and 7 others. The majority were diagnosed during the same inpatient stay by recognition of typical drain appearance and increased volume. Three cases were diagnosed during outpatient visits with increased abdominal phadenectomy to prevent morbidity.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19), and has caused more than 80 million infections and 1.7 million deaths worldwide. Although it is primarily a respiratory virus, SARS-CoV-2 also has extra-pulmonary effects. Pancreatic injury and cases of acute pancreatitis (AP) have been recognized and attributed to SARS-CoV-2, but the mechanisms of pancreatic injury are still a subject of debate. There is also controversy on whether SARS-CoV-2 can cause AP or if it is an epiphenomenon.
To review and to explore the relationship between SARS-CoV-2 infection and AP, and to provide an overview of the existing literature on possible mechanisms of SARS-CoV-2-induced pancreatic lesion.
A systematic review was conducted in accordance with PRISMA guidelines for papers on SARS-CoV-2 infection and AP. A narrative review on possible mechanisms of SARS-CoV-2-induced pancreatic lesion was also performed.
A literature review reo entities and their theragnostic significance.
AP should be considered in COVID-19 patients, especially in those exhibiting abdominal pain and systematic, and complete reporting of these cases should be general practice. However, there is still insufficient evidence showing that COVID-19 can cause AP or negatively impact prognosis. Additional studies are needed to clarify the relationship between these two entities and their theragnostic significance.
Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. PF-06826647 Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice.
To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an
porcine model basic study.
Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and sec/complete resection rate and perforation rate (complete resection, 93.8%
87.5%,
= 0.67; perforation, 0%
3.1%,
= 1). Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD (odds ratio = 10.2; highest among factors).
Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.
Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.