Focused Resonance Nano-permeabilization (FORN) (US Patent 9,616, 245 B2-Apr 11th 2017) enables the targeted delivery of chemo-therapeutic molecules using a safe, non-invasive, whole-body therapeutic device. The prototype device houses a gantry with specialized, near field, radio-frequency (RF) antennae and guns to deliver instantaneous, magnetic resonance. Drug focusing and delivery was enabled using FORN in a patient with advanced, loco-regionally recurrent, metastatic, nasopharyngeal carcinoma (NPC). Nonionizing, safe, extraneous-source radio-frequencies (RF) were delivered in the presence of an instantaneous magnetic field, to create temporary drug molecular weight-specific nanopores in the cell membrane of target lesions, concurrently with systemic chemotherapy. The high frequency RF is timed and delivered to regions of interest (ROIs) to span peak plasma concentrations of infused chemotherapeutic drugs over multiple treatment cycles. FORN-enabled chemotherapy-related adverse event evaluation and tumor response based on PERCIST 1.0 reflected improved clinical, anatomical and metabolic outcomes and significantly reduced myelosuppression in the patient who received 6+1 Cycles of combination chemotherapy, over an extended period of time. Functional Assessment of Cancer Treatment-Head & Neck (FACT-H&N) / Quality of Life (QoL) and Karnofsky Performance Status (KPS) reflected overall patient well-being.

Tumor markers such as beta Human Chorionic Gonadotropin (bHCG) and Carboxyhydrate Antigen 19-9 (CA19-9) have long been associated with bladder cancer and although their expression is associated with poorer oncological outcomes, they have little role in the routine clinical management of this disease. Recent advances in engineered antibody technology have lead to renewed interest in these markers as potential targets for new therapeutics. Here we report the case of a patient with locally advanced bladder cancer and the response of serum bHCG and CA19-9 to endoscopic resection and then radical cystectomy and serves to highlight how these tumor markers might be used to measure treatment effect.

It is well established that tumors are unable to grow beyond a certain size (1-2 mm) unless they acquire their own blood supply via angiogenesis. Also, angiogenesis helps tumors to invade adjacent tissues and metastasize to distant sites [1]. Therefore, it has been postulated that interfering with the blood supply using anti-angiogenic therapies will destroy the tumor [2]. However, there is an emerging alternative concept that depriving the tumor of its blood supply interferes with the delivery of chemotherapeutic agents to the tumor and creates an unfavorable hypoxic environment that compromises the action of radiotherapy [3]. This concept was supported by the modest responses to anti-angiogenic therapies in clinical trials and the lack of any impact on patient’s survival when antiangiogenic drugs are administered as single agents [4]. Although, Hurwitz et al. [5] have shown that combining the antiangiogenic drug, bevacizumab with chemotherapy significantly improved survival among metastatic colorectal cancer patients. Still, other studies demonstrated reductions in tumor concentrations of chemotherapy or effectiveness of radiotherapy when antiangiogenic drugs were co-administered [6-8]. Even when antiangiogenic drugs yielded significant effects on the growth of some tumors such as renal cell carcinoma, cervical cancer, and ovarian cancer, they failed to demonstrate significant improvements in patients’ survival [9,10]. Furthermore, complete resistance to antiangiogenic therapies has been reported for prostate and pancreatic adenocarcinoma and melanoma that might be attributed to the redundant involvement of several angiogenic factors that are difficult to be targeted by a single anti-angiogenic agent in some tumors [11-13]. To explain this inconsistency, further research is needed for better understanding of the underlying cellular and molecular mechanisms of tumor vascularization and its interaction with cancer therapies in different tumor beds.

Cancers treated with Vincristine and vinblastine include: acute leukemia, Hodgkins and non-Hodgkins lymphoma, neuroblastoma, rhabdomyosarcoma, Ewings sarcoma, Wilms tumor, multiple myeloma, chronic leukemias, thyroid cancer, brain tumors, non-small cell lung cancer, bladder cancer, melanoma, and testicular cancer and It is also used to treat some blood disorders. It is given by injection into a vein. Vincristine and vinblastine exhibit differential activity against tumors and normal tissues. In this work, a number of cultured cell lines were assayed for their sensitivity to the antiproliferative and cytotoxic effects of the two drugs following short-term (4 hr) or during continuous exposures. Differential activity was not seen when cells were subjected to continuous exposures. The concentrations of Vincristine and vinblastine, respectively, that inhibited growth rates by 50% were: mouse leukemia L1210 cells, 4.4 and 4.0nw; mouse lymphoma S49 cells, 5 and 3.5nM; mouse neuroblastoma cells, 33 and 15nw; HeLa cells, 1.4 and 2.6nw; and human leukemia HL-60 cells, 4.1 and 5.3nM. In contrast, differential toxicity was seen when cells were subjected to 4-hr exposures and transferred to drug-free medium: the 50% growth-inhibitory concentrations for Vincristine and vinblastine, respectively, for inhibition (a) of proliferation of L1210 cells were 100 and 380nM and of HL-60 cells were 23 and 900nM and (b) of colony formation of L1210 cells were 6 and >600nM and of HeLa cells were 33 and 62nM. Uptake and release of [3H]-vincristine and [3H]-vinblastine were examined in L1210 cells under the conditions of growth experiments. Uptake of both drugs was dependent on the pH of culture media, and significantly greater amounts of [3H]vinblastine than of [3H] vincristine were associated with cells after 4-hr exposures to equal concentrations of either drug. When cells were transferred to drug-free medium after 4-hr exposures, vinblastine was released much more rapidly from cells than was Vincristine, and by 0.5hr after resuspension of cells, the amount of Vincristine associated with the cells was greater than the amount of vinblastine and remained so for up to at least 6hrs.

The introduction of three-dimensional (3D) tumor cultures has revolutionized anticancer drug research as these cultures allow for the study of drug resistance mechanisms that cannot be explored in traditional two dimensional (2D) monolayer cultures. Discoveries in the 3D tumor culture field suggest that individualized drug sensitivity testing of solid tumor specimens through the establishment and use of 3D tumor cell cultures following tissue collection will become a routine service offered by modern tissue repositories as they expand from their traditional research role to active participation in personalized medicine. Unfortunately, most information related to 3D tumor cultures comes from studies using established tumor cell lines rather than primary tumor cultures. However, accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine. There is only very limited information available concerning technologies and standard operating procedures for the efficient and routine isolation and processing of primary tumor cells for the establishment of 3D tumor cultures from solid tumor specimens. The purpose of this work was to review experimental data from the literature that may provide relevant information concerning the isolation and processing of primary tumor cells for the establishment of 3D tumor cultures. Information reviewed here may help bio repositories in the development and standardization of technologies and standard operating procedures related to the use of 3D tumor cultures.