A common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice.

Objective: Genome wide association studies have identified an exon 6 deletion variant that associates with increased risk of pancreatic cancer. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in , the mouse orthologue of .

Design: We used CRISPR/Cas9 to introduce a 707bp deletion in encompassing exon 6 ( ).

Facial palsy after administration of immune checkpoint inhibitors: case report, literature review and clinical care management.

Neurological immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI) are rare complications of immunotherapy, particularly dreadful for patients and clinical teams. Indeed, neurological irAEs are potentially severe and their diagnosis require prompt recognition and treatment. Additionally, the spectrum of neurological irAEs is broad, affecting either neuromuscular junction, peripheral or central nervous system.

Management and outcomes of brain metastases from pancreatic adenocarcinoma: a pooled analysis and literature review.

Background: Brain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes.

Aim: We aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature.

Methods: We conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1).

Piecemeal Resection for Large Colorectal Adenomas Remains Essential in 2022: A Single-Center Experience in a Tertiary French Center.

Background And Aims: Colorectal lesions measuring greater than 20 mm are unsuitable for en bloc endoscopic mucosal resection (EMR): piecemeal EMR (PM-EMR) and endoscopic submucosal dissection (ESD) are needed. The European Society of Gastrointestinal Endoscopy (ESGE) recommends ESD only for microinfiltrative lesions, although Japanese teams perform en bloc ESD for all lesions. We report the outcomes obtained in our endoscopy unit for these lesions and assess the hybrid "knife-assisted piecemeal EMR" (KAPM-EMR) technique.

Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records.

Background: Dysthyroidism (DT) is a common toxicity of immune checkpoint inhibitors (ICIs) and prior work suggests that dysthyroidism (DT) might be associated with ICI efficacy.

Patients And Methods: ConSoRe, a new generation data mining solution, was used in this retrospective study, to extract data from electronic patient records of adult cancer patients treated with ICI at Institut Paoli-Calmettes (Marseille, France). Every DT was verified and only ICI-induced DT was retained.

Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study.

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography techinics.

Impact of fiducial markers placement on the delineation of target volumes in radiation therapy for oesophageal cancer: FIDUCOR study.

Purpose: This prospective monocentric phase II study (FIDUCOR-study, NCT02526134) aimed to assess the impact of fiducial markers (FMs) implantation on conformal chemo-radiation therapy (CRT) planning in oesophageal carcinoma (EC) patients.

Methods/materials: Fifteen EC patients were enrolled in the study. Each patient underwent two simulation CT-scans before (CT1) and after (CT2) FMs implantation, in the same position.

Mass Cytometry Reveals Classical Monocytes, NK Cells, and ICOS+ CD4+ T Cells Associated with Pembrolizumab Efficacy in Patients with Lung Cancer.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of non-small cell lung cancer (NSCLC), but predictive biomarkers of their efficacy are imperfect. The primary objective is to evaluate circulating immune predictors of pembrolizumab efficacy in patients with advanced NSCLC.

Experimental Design: We used high-dimensional mass cytometry (CyTOF) in baseline blood samples of patients with advanced NSCLC treated with pembrolizumab.

Case-Matched Comparison of Functional and Quality of Life Outcomes of Local Excision and Total Mesorectal Excision Following Chemoradiotherapy for Rectal Cancer.

Background: Neoadjuvant chemoradiotherapy followed by radical surgery is the standard curative treatment for mid- to low-rectal cancer. However, the combination of these treatments may affect patients' GI and genitourinary functions and their quality of life. In the cases of good clinical response to neoadjuvant treatment, local excision is a rectal sparing strategy that would limit these side effects.

Pasireotide for Refractory Hypoglycemia in Malignant Insulinoma- Case Report and Review of the Literature.

Malignant insulinomas are functional neuroendocrine tumors of the pancreas and the primary cause of tumor-related hypoglycemia. Malignant insulinoma is rare and has a poor prognosis. We report a case of metastatic malignant insulinoma in a 64-year-old female patient with severe and refractory hypoglycemia.

Genomic analysis of paired IDHwt glioblastomas reveals recurrent alterations of MPDZ at relapse after radiotherapy and chemotherapy.

Purpose: We aimed to identify genomic drivers of glioblastoma inevitable recurrence.

Methods: Ten pairs of initial and recurrent frozen IDHwt glioblastoma samples were screened by CGH Array. Next Generation Sequencing (NGS) was then performed on an enriched cohort of 19 pairs.

Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report.

Immune checkpoint inhibitors (ICI) reinvigorate the immune system to recognize and destroy tumor cells. Because of this biological mechanism, patients might develop autoimmune toxicities, notably in the digestive tract (most frequently, hepatitis or colitis). A 70-year-old man with relapsed mesothelioma was treated with nivolumab in 3rd line.

Endoscopic Ultrasound-Guided Radiofrequency Ablation as an Future Alternative to Pancreatectomy for Pancreatic Metastases from Renal Cell Carcinoma: A Prospective Study.

Background: Pancreatic metastases (PM) from renal cell carcinoma (RCC) are rare, are associated with favorable outcomes and are usually handled by surgery or VEGFR inhibitors, which both have side effects. Endoscopic Ultrasound (EUS)-guided radiofrequency ablation (RFA) is an innovative approach to treat focally deep metastases and could be a relevant technique to control PM from RCC.

Methods: This monocentric, prospective study aimed to evaluate the safety and efficacy of EUS-RFA to treat PM.

Soluble BTN2A1 Is a Potential Prognosis Biomarker in Pre-Treated Advanced Renal Cell Carcinoma.

The development of immune checkpoint inhibitors (ICI) has dramatically changed the landscape of therapies for metastatic renal cell carcinoma. However, many patients do not benefit from such therapy and prognostic or predictive validated biomarker validated for ICI are still needed to better select and treat patient. Plasmatic soluble immune checkpoints have been described as potential immune biomarkers in hematological malignancies and solids tumors, then, we would like to explore the prognostic value of different soluble immune checkpoints in patients with mRCC treated with nivolumab after TKI.

EB1 Restricts Breast Cancer Cell Invadopodia Formation and Matrix Proteolysis via FAK.

Regulation of microtubule dynamics by plus-end tracking proteins (+TIPs) plays an essential role in cancer cell migration. However, the role of +TIPs in cancer cell invasion has been poorly addressed. Invadopodia, actin-rich protrusions specialized in extracellular matrix degradation, are essential for cancer cell invasion and metastasis, the leading cause of death in breast cancer.

Adoptive Cell Therapy in Hepatocellular Carcinoma: Biological Rationale and First Results in Early Phase Clinical Trials.

The mortality of hepatocellular carcinoma (HCC) is quickly increasing worldwide. In unresectable HCC, the cornerstone of systemic treatments is switching from tyrosine kinase inhibitors to immune checkpoints inhibitors (ICI). Next to ICI, adoptive cell transfer represents another promising field of immunotherapy.

Medical Treatment of Lung Cancer: Can Immune Cells Predict the Response? A Systematic Review.

The landscape for medical treatment of lung cancer has irreversibly changed since the development of immuno-oncology (IO). Yet, while immune checkpoint blockade (ICB) revealed that T lymphocytes play a major role in lung cancer, the precise dynamic of innate and adaptive immune cells induced by anticancer treatments including chemotherapy, targeted therapy, and/or ICB is poorly understood. In lung cancer, studies evaluating specific immune cell populations as predictors of response to medical treatment are scarce, and knowledge is fragmented.

Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020.

Almost half of the new cases of colorectal cancer concern patients aged ≥70 years. However, very few clinical trials have specifically included older patients. As a consequence, the treatment of these patients is controversial because the balance between clinical benefits and toxicities remains uncertain.

A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells.

Metastatic progression is the leading cause of mortality in breast cancer. Invasive tumor cells develop invadopodia to travel through basement membranes and the interstitial matrix. Substantial efforts have been made to characterize invadopodia molecular composition.

Evaluation of gemcitabine efficacy after the FOLFIRINOX regimen in patients with advanced pancreatic adenocarcinoma.

To evaluate gemcitabine efficacy in advanced pancreatic cancer patients after the FOLFIRINOX regimen.Patients with locally-advanced or metastatic pancreatic adenocarcinoma from French and Canadian centers, who were treated with the first-line FOLFIRINOX regimen (FFX L1), followed by gemcitabine monotherapy as a second-line treatment (GEM L2), were retrospectively evaluated. Statistical analyses were performed on the demographic, toxicity, and response rate data.

A scoring system to guide the decision for a new systemic treatment after at least two lines of palliative chemotherapy for metastatic cancers: a prospective study.

Purpose: A four-parameter score has been identified as associated with overall survival (OS) in patients with advanced cancer with an estimated survival inferior to 6 months. Here, we tested its prognostic value for OS in patients who had received more than two lines of systemic therapy.

Methods: We prospectively enrolled patients with advanced cancer who were going to receive a third or more therapeutic line outside classical clinical guidelines.

Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era.

Background: Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs.

Patients And Methods: Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed.