Critical Reviews in Oncogenesis最新文献

When selected tumor cells in a large in vitro population are exposed to ionizing radiation, they can send pro-survival signals to non-exposed counterparts (bystander cells). If there is no physical contact between irradiated and bystander cells, the latter respond to mediators from targeted cells that diffuse through the medium. One such mediator is known to be nitric oxide (NO). It was recently discovered that non-ionizing anti-tumor photodynamic therapy (PDT) can also elicit pro-survival/expansion bystander effects in a variety of human cancer cells. A novel silicone ring-based approach was used for distinguishing photodynamically-targeted cells from non-targeted bystanders. A key finding was that NO from upregulated iNOS in surviving targeted cells diffused to the bystanders and caused iNOS/NO upregulation there, which in turn stimulated cell proliferation and migration. The intensity of these responses depended on the extent of iNOS/NO induction in targeted cells of different cancer lines. Moreover, the responses could be replicated using NO from the chemical donor DETA/NO. This review will focus on these and related findings, their negative implications for clinical PDT, and how these might be averted by using pharmacologic inhibitors of iNOS activity or transcription.

Oral cancer (OC) is increasing worldwide, and it is mostly present to clinic in the late-stage of disease. Cancer of the lips, tongue, hard palate, upper and lower gingiva, buccal mucosa, and retromolar trigone are all included in the category of oral cavity cancer. Disease symptomatology and pathological grading decides the course of treatment. Several treatment modalities either alone in combinations may be utilized for oral squamous cell carcinoma (OSCC), including surgery, radiotherapy (external beam radiotherapy/brachytherapy), and adjuvant systemic therapy (chemotherapy or immunotherapy). Cancer patients also face a greater risk of oral side effects from chemotherapy, such as slowed tissue healing, bone, and salivary gland damage and disintegration, and disruption of the normal bacterial balance in the mouth. Consequently, the economic burden of the salivary gland, oral cavity, and oropharyngeal cancers must be also known for budget allocation, designing different programs and management strategies targeting oral cancers by any healthcare institutes. This article provides a summary of the most recent research that supports the use of chemotherapy for patients with advanced illness both alone and in conjunction with radiation including its adverse events and cost burden for oral cancers.

Oral cancer (OC) has emerged as a major medical and social issue in many industrialized nations due to the high death rate. It is becoming increasingly common in people under the age of 45, although the underlying causes and mechanisms of this increase remain unclear. Melatonin, as a pleiotropic hormone, plays a pivotal role in a wide variety of cellular and physiological functions. Mounting evidence supports melatonin's ability to modify/influence oral carcinogenesis, help in the reduction of the incidence of OC, and increase chemo- and radiosensitivity. Despite its potential anti-carcinogenic effects, the precise function of melatonin in the management of OC is not well understood. This review summarizes the current knowledge regarding melatonin function in anti-carcinogenesis mechanisms for OC. In addition, clinical assessment and the potential therapeutic utility of melatonin in OC are discussed. This review will provide a basis for researchers to create new melatonin-based personalized medicines for treating and preventing OC.

The role of nitric oxide (NO) in cancer has been a continuous challenge and particularly the contradictory findings in the literature reporting NO with either anti-cancer properties or pro-cancer properties. This dilemma was largely resolved by the level of NO/inducible nitric oxide synthase in the tumor environment as well as other cancer-associated gene activations in different cancers. The initial findings on the role of NO as an anti-cancer agent was initiated in the late 1990's in Dr. Larry Keefer's laboratory, who had been studying and synthesizing many compounds with releasing NO under different conditions. Using an experimental model with selected NO compounds they demonstrated for the first time that NO can inhibit tumor cell proliferation and sensitizes drug-resistant cancer cells to chemotherapy-induced cytotoxicity. This initial finding was the backbone and the foundation of subsequent reports by the Keefer's laboratory and followed by many others to date on NO-mediated anti-cancer activities and the clinical translation of NO donors in cancer therapy. Our laboratory initiated studies on NO-mediated anti-cancer therapy and chemo-immuno-sensitization following Keefer's findings and used one of his synthesized NO donors, namely, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate), throughout most of our studies. Many of Keefer's collaborators and other investigators have reported on the selected compound, O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl] diazen-1-ium-1,2-diolate (JS-K), and its therapeutic role in many tumor model systems. Several lines of evidence that investigated the treatment with NO donors in various cancer models revealed that a large number of gene products are modulated by NO, thus emphasizing the pleiotropic effects of NO on cancers and the identification of many targets of therapeutic significance. The present review reports historically of several examples reported in the literature that emanated on NO-mediated anti-cancer activities by the Keefer's laboratory and his collaborators and other investigators including my laboratory at the University of California at Los Angeles.

Cutaneous melanoma (CM) incidence has dramatically increased in the last years. Early diagnosis is of paramount importance in terms of prognosis. Artificial Intelligence (AI) tools are being proposed for clinicians and pathologists as an adjunct support in the diagnostic process. We described herein an overview of the most important parameters that a potential AI tool should take into consideration in histopathology to evaluate a skin lesion. First of all, recognition of a melanocytic or non-melanocytic nature. Furthermore, melanocytic lesions should be stratified according to at least four parameters: silhouette and asymmetry; identification and spatial distribution of the cells; mitosis count; presence of ulceration. According to the number of parameters the AI tools might stratify the risk of CM and prioritize the pathologist's work.

Precision treatment requires precision imaging. With the advent of various advanced techniques in head and neck cancer treatment, imaging has become an integral part of the multidisciplinary approach to head and neck cancer care from diagnosis to staging and also plays a vital role in response evaluation in various tumors. Conventional anatomic imaging (CT scan, MRI, ultrasound) remains basic and focuses on defining the anatomical extent of the disease and its spread. Accurate assessment of the biological behavior of tumors, including tumor cellularity, growth, and response evaluation, is evolving with recent advances in molecular, functional, and hybrid/multiplex imaging. Integration of these various advanced diagnostic imaging and nonimaging methods aids understanding of cancer pathophysiology and provides a more comprehensive evaluation in this era of precision treatment. Here we discuss the current status of various advanced imaging techniques and their applications in head and neck cancer imaging.