Real world clinical experience using daily intelligence-assisted online adaptive radiotherapy for head and neck cancer.

Background: Adaptive radiation therapy (ART) offers a dynamic approach to address structural and spatial changes that occur during radiotherapy (RT) for locally advanced head and neck cancers. The integration of daily ART with Cone-Beam CT (CBCT) imaging presents a solution to enhance the therapeutic ratio by addressing inter-fractional changes.

Methods: We evaluated the initial clinical experience of daily ART for patients with head and neck cancer using an online adaptive platform with intelligence-assisted workflows on daily CBCT.

Safety and Efficacy of Oral Human Parathyroid Hormone (1-34) in Hypoparathyroidism: An Open-Label Study.

The standard treatment of primary hypoparathyroidism (hypoPT) with oral calcium supplementation and calcitriol (or an analog), intended to control hypocalcemia and hyperphosphatemia and avoid hypercalciuria, remains challenging for both patients and clinicians. In 2015, human parathyroid hormone (hPTH) (1-84) administered as a daily subcutaneous injection was approved as an adjunctive treatment in patients who cannot be well controlled on the standard treatments alone. This open-label study aimed to assess the safety and efficacy of an oral hPTH(1-34) formulation as an adjunct to standard treatment in adult subjects with hypoparathyroidism.

Oral Insulin Delivery in a Physiologic Context: Review.

Insulin remains indispensable to the treatment of diabetes, but its availability in injectable form only has hampered its timely and broader use. The development of an oral insulin remains an ultimate goal to both enhance ease of use, and to provide therapeutic advantages rooted in its direct delivery to the portal vein and liver. By mimicking the physiological path taken by pancreatic insulin, oral insulin is expected to have a distinct effect on the hepatic aspect of carbohydrate metabolism, hepatic insulin resistance, and, at the same time, avoid hyperinsulinemia and minimize the risk of hypoglycemia.

Bile acid: a potential inducer of colon cancer stem cells.

Background: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer.

Methods: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs.

Lessons learned from the clinical development of oral peptides.

The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these oral formulations.

Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study.

Unlabelled: The unpredictable behavior of uncontrolled type 1 diabetes often involves frequent swings in blood glucose levels that impact maintenance of a daily routine. An intensified insulin regimen is often unsuccessful, while other therapeutic options, such as amylin analog injections, use of continuous glucose sensors, and islet or pancreas transplantation are of limited clinical use. In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state.

Novel glucagon-like peptide-1 analog delivered orally reduces postprandial glucose excursions in porcine and canine models.

Background: Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence.

Open-label study to assess the safety and pharmacodynamics of five oral insulin formulations in healthy subjects.

Aim: Orally delivered insulin is predicted to bear therapeutic advantages in diabetes management when compared to injectable insulin, because of its ability to mimic the natural route of endogenous insulin secreted by the pancreas into the portal vein and directly to the liver. Oramed Pharmaceuticals is developing an oral insulin product which consists of unmodified recombinant human insulin combined with adjuvants that protect it from enzymatic degradation in the gastrointestinal tract and promote its absorption from the gut. The aim was to determine the optimal adjuvants to insulin ratio which can provide for the best pharmacodynamic profile, while maintaining the safety of the product.

Oral insulin: the rationale for this approach and current developments.

Insulin remains the most effective and durable hypoglycemic agent for the treatment of diabetes. The addition of an effective oral insulin dosage form to the antidiabetes armamentarium may have significant benefits in terms of fostering compliance and adherence among patients, as well as physiologic advantages due to the fact that such a dosage form replicates the natural route of insulin secretion and absorption through the portal vein and targets the liver directly. Several companies have developed technological platforms that protect polypeptides and proteins from enzymatic hydrolysis, enable their transport across the epithelial lining, and promote their absorption from the gastrointestinal tract.

Pharmacokinetics and pharmacodynamic effects of oral GLP-1 and PYY3-36: a proof-of-concept study in healthy subjects.

This proof-of-concept study was performed in order to establish the pharmacokinetics and pharmacodynamics of increasing oral doses of the satiety peptides glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY3-36). Six healthy male subjects were given oral doses of either a placebo or GLP-1 in a dose-escalating schedule (doses of 0.5, 1.

Oral heparin: status review.

Unfractionated heparin and low molecular weight heparin are the most commonly used antithrombotic and thromboprophylactic agents in hospital practice. Extended out-of-hospital treatment is inconvenient in that these agents must be administered parenterally. Current research is directed at development of a safe and effective oral antithrombotic agent as an alternative for the effective, yet difficult to use vitamin K antagonists.

The physiological rationale for oral insulin administration.

Insulin remains the most effective and durable drug in the armamentarium for the treatment of advanced-stage diabetes. Nevertheless, clinical studies have shown that even on insulin treatment, a significant percentage of patients fail to attain lasting glycemic control. Well-recognized reasons for this failure include issues related to patients' noncompliance with an injectable drug and the late stage at which insulin is prescribed, but less explicit reasons related to the nonphysiological way insulin is currently administered are equally important.

A novel per-oral insulin formulation: proof of concept study in non-diabetic subjects.

Aims: The aim of our study was to examine the absorption of insulin from the gastrointestinal (GI) tract, using a novel oral formulation-adding a delivery agent SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) in combination with insulin.

Methods: Capsules containing insulin and SNAC, in various combinations, were administered orally, as a single dose, to 12 non-diabetic subjects and four control subjects (receiving SNAC or insulin only) in order to assess its biological effect and safety. Plasma glucose levels, insulin and C-peptide concentrations, as well as SNAC levels, were determined, at timed intervals up to 4 h.

Adoptive cellular immunotherapy for the treatment of malignant gliomas.

Unlabelled: The median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reoperation can extend the median survival an additional 26-32 weeks. We have developed an aggressive treatment program that utilizes low doses of interleukin-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via an indwelling catheter placed into the surgical resection cavity.

Treatment of refractory recurrent malignant glioma with adoptive cellular immunotherapy: a case report.

We report the successful treatment of a patient with recurrent malignant glioma with adoptive cellular immunotherapy. The patient is a young adult with recurrent progressive disease refractory to aggressive multi-modality therapy including repetitive surgical resection, radiation, radiosurgery and chemotherapy. He received multiple courses of local administration of autologous lymphokine-activated killer (LAK) cells in combination with a low dose of interleukin-2 (IL-2) through an Ommaya reservoir-catheter system.

Lumbar stenosis: a clinical review.

A brief history, classification, clinical presentation, and pertinent anatomy of spinal stenosis is presented. A thorough understanding of the etiology, pathologic features, and the correlation between symptoms and precisely where the thecal sac and nerve root impingement occurs is essential to interpret imaging studies and plan appropriate treatment.

Enhancing the uptake of chemotherapeutic drugs into tumors using an "artificial lymphatic system".

This paper presents findings from uptake studies to evaluate the ability of an "artificial lymphatic system" (ALS) to enhance large and small molecular weight drug transport into solid tumors and the therapeutic effect of the additional drug on their growth. These studies also served to test the effectiveness of an implantable multidrain ALS. Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin.

"Artificial lymphatic system": a new approach to reduce interstitial hypertension and increase blood flow, pH and pO2 in solid tumors.

A mechanical drainage system, the "artificial lymphatic system" (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration.

Surgical treatment of brain metastases from melanoma: a retrospective study of 91 patients.

Object: Reports on the surgical treatment of brain metastases from melanoma in a large group of patients are sparse. The goal of this paper is to review the surgical experience in a series of 91 patients with brain metastases from primary melanoma treated at a single institution.

Methods: Seven hundred eighty patients underwent resection of brain metastases at Memorial Sloan-Kettering Cancer Center between 1974 and 1994.