A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening.

Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs are benign lesions: they do not undergo malignant transformation or metastasize. Nevertheless, they can cover a significant proportion of the body, with some individuals developing hundreds to thousands of lesions.

Preclinical Efficacy of the Antibody-Drug Conjugate CLDN6-23-ADC for the Treatment of CLDN6-Positive Solid Tumors.

Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6-23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker.

A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids.

Tumor organoids maintain cell-cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications. Although organoids are in principle amenable to high-throughput screenings, progress has been hampered by technical constraints and extensive manipulations required by current methods.

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons.

Background: The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC.

Stapling technique for performing Billroth II anastomosis after distal gastrectomy.

The circular stapling technique has been widely applied for gastrointestinal anastomosis in gastrectomies (open or laparoscopic) for distal gastric cancers. We describe this method for use in performing Billroth II anastomosis in distal gastrectomies. From 2002-2009, we report the results following the use of the circular stapling technique performed in 520 patients at a single institution.

A TCR targeting the HLA-A*0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer.

Adoptive immunotherapy using TCR-engineered PBLs against melanocyte differentiation Ags mediates objective tumor regression but is associated with on-target toxicity. To avoid toxicity to normal tissues, we targeted cancer testis Ag (CTA) MAGE-A3, which is widely expressed in a range of epithelial malignancies but is not expressed in most normal tissues. To generate high-avidity TCRs against MAGE-A3, we employed a transgenic mouse model that expresses the human HLA-A*0201 molecule.

Successful treatment of melanoma brain metastases with adoptive cell therapy.

Purpose: To determine the objective response rate and response duration of melanoma brain metastases to adoptive cell therapy (ACT) with autologous antitumor lymphocytes plus interleukin-2 following a lymphodepleting preparative regimen.

Methods: Between 2000 and 2009, 264 patients with metastatic melanoma received ACT, consisting of cyclophosphamide and fludarabine with or without total body irradiation, followed by the infusion of autologous tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor (TCR) that recognized the melanocyte differentiation antigens gp-100 or MART-1. From this group, 26 patients were retrospectively identified to have had untreated brain metastases and extracranial disease before receiving ACT.

CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma.

Purpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched "young" TIL.

Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE.

Phospholipase C gamma 1 (PLC-gamma 1) hydrolyses phosphatidylinositol-4,5-bisphosphate to the second messengers inositol-1,4,5-trisphosphate and diacylglycerol. PLC-gamma 1 also has mitogenic activity upon growth-factor-dependent tyrosine phosphorylation; however, this activity is not dependent on the phospholipase activity of PLC-gamma 1, but requires an SH3 domain. Here, we demonstrate that PLC-gamma 1 acts as a guanine nucleotide exchange factor (GEF) for PIKE (phosphatidylinositol-3-OH kinase (PI(3)K) enhancer).