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Purpose:. Emerging evidence indicates that gut microbiome plays a crucial role in the cancer pathogenesis. Although Fusobacterium nucleatum ( F. nucleatum ) is associated with poor prognosis in multiple cancers, its clinical significance in predicting response to chemotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. Experimental Design:. The F. nucleatum levels were quantified by qPCR assays in tumor tissues from 551 patients with ESCC from two independent cohorts, including 101 patients who received neoadjuvant chemotherapy prior to curative resection. Associations between F. nucleatum burden and recurrence-free survival (RFS), as well with chemotherapeutic response were evaluated using response evaluation
Purpose:. Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express mesothelin, a tumor-associated antigen highly expressed in MPM. CRS-207 induces antitumor immune responses and increases susceptibility of neoplastic cells to immune-mediated killing. Patients and Methods:. Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were enrolled in this multicenter, open-label phase Ib study. They received two priming infusions of 1 x 10 9 CFU CRS-207, followed by pemetrexed/cisplatin chemotherapy, and CRS-207 booster infusions. Primary objectives were safety and induction of immune response. Secondary/explo.
Purpose:. Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1–35 years after CBC and evaluate genetic contributions to these levels. Experimental Design:. Eligible TCS given 300 or 400 (±15) mg/m 2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using.
Purpose:. Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX + CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods:. Patients wit.
Purpose:. Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed. Experimental Design:. Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively. Results:. We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key hist.
Purpose:. Perivascular epitheliod cell tumors (PEComas) are rare mesenchymal neoplasms for which the role of systemic treatments is not established as there are no published prospective clinical trials or sufficiently large retrospective case series. The aim of this study is to clarify the activity of conventional chemotherapy and biological agents in advanced/metastatic PEComas. Experimental Design:. This was an observational, retrospective, international study that included patients with advanced/metastatic PEComa treated with systemic therapy at 5 European sarcoma reference centers and within the Italian Rare Cancer Network. Survival analyses were performed using the Kaplan–Meier method and the Cox hazards regression models. Results:. A tot.
Purpose:. After cisplatin-based neoadjuvant chemotherapy (NAC), 60% of patients with muscle-invasive bladder cancer (MIBC) still have residual invasive disease at radical cystectomy. The NAC-induced biological alterations in these cisplatin-resistant tumors remain largely unstudied. Experimental Design:. Radical cystectomy samples were available for gene expression analysis from 133 patients with residual invasive disease after cisplatin-based NAC, of whom 116 had matched pre-NAC samples. Unsupervised consensus clustering (CC) was performed and the consensus clusters were investigated for their biological and clinical characteristics. Hematoxylin & Eosin and IHC on tissue microarrays were used to confirm tissue sampling and gene expression an.
Purpose:. The histone deacetylase (HDAC) inhibitor panobinostat potentiates anthracycline and cytarabine cytotoxicity in acute myeloid leukemia (AML) cells. We hypothesized that panobinostat prior to and during induction chemotherapy would be tolerable and augment response in patients showing increased histone acetylation. Patients and Methods:. Patients received panobinostat 20–60 mg oral daily on days 1, 3, 5, and 8 with daunorubicin 60 mg/m 2 /day intravenously on days 3 to 5 and cytarabine 100 mg/m 2 /day intravenously by continuous infusion on days 3 to 9 ("7+3"). Peripheral blood mononuclear cells (PBMCs) were isolated for HDAC expression and histone acetylation changes. Results:. Twenty-five patients ages 60–85 years (median age, 69) we.
Purpose:. Hormone receptor–positive/HER2-negative (HR + /HER2 – ) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR + /HER2 – breast tumors. Experimental Design:. HR + /HER2 – breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8 + cells, CD68 + cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed. Results:. Ninety-

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