Lupine Publishers: Soil Texture of Nesting Sites and Breeding Populat...

Lupine Publishers: Soil Texture of Nesting Sites and Breeding Populat...: Lupine Publishers- Environmental and Soil Science Abstract Investigating the breeding population and soil texture of breeding ...

Lupine Publishers: Change of Evaporations Leads to Climate Change

Lupine Publishers: Change of Evaporations Leads to Climate Change: Lupine Publishers- Environmental and Soil Science Short Communication The basis of all floods and droughts is water, its e...

Lupine publishers | Head Cancer and Metastasic Neck. What Have We Advanced in the Last Years?

Lupine Publishers | Open Access Journal of Oncology and Medicine

Abstract

In 2012, 5.210 new cases of head and neck tumors were estimated in the USA, with an increasing incidence due to tobacco and alcohol habits in the population. A large percentage of the cases debut as a locally advanced disease, so control of the disease is key and we look for the best therapeutic strategy to achieve good survival rates while maintaining quality of life. We present the case of a 60-year-old patient in which our objectives to be presented are the assessment of comorbidity, toxicity and survival.

Clinical Case

A 60-year-old man without medical illnesses to be highlighted. He came to the emergency room in July 2016 due to injury at the cervical level of 1 month of evolution, with progressive growth and breathness, with also difficulty for eating. Also asthenia, anorexia and loss of weight not quantified in the last month.
Physical Examination: Weight 42 kg Head and Neck: mass of hard consistency of approximately 10 cm in diameter in the cervical left region that seems to deflect trachea. Pulmonary auscultation: generalized hypoventilation with some expiratory wheeze.

Additional Tests

a. Fibroscopy (August 2016) ulcerated lesion from right vallecula to mouth of Killian. Paresis of both vocal cords.
b. PET-CT (August 2016): Extensive tumor in pharynxlarynx- esophagus (> 6 cm) Lymph nodes in left IB-II spaces (> 6 cm). If confirmed, carcinoma would correspond to T3 N3 (stage IVB) (Figure 1).
c. Laryngeal Biopsy: Moderately differentiated and keratinizing squamous cell carcinoma.

Figure 1: PET-CT August 2016: Pathological adenopathies> 6 cm in left IB-II spaces

So, confirmed Squamous cell carcinoma stage cT4N3 Mx.The case is presented in the Tumor Committee, deciding treatment with Chemoradiotherapy and 1 cycle of Docetaxel+ Cisplatin (60% dose reduction because of frailty/ malnutrition) previous to induction due to the large tumor volume and waiting for start radiotherapy. Tracheotomy is performed prior to starting because of the risk of airway obstruction and also gastrostomy is placed for nutritional support.
On 31th August 2016 the patient starts on RT concomitantly to Cisplain ( receiving 2 cycles on 12.09.2016 and 10.10.2016 and 70 Gy) During the treatment, he achieves a good general condition until January 2017, when he goes to Otolaryngology Clinics referring dysphagia again although he maintains weight in 51 kg. PET-CT is performed: disease progression with soft tissue increase in the pharyngoesophageal junction despite the good response of cervical adenopathies and the partial response of the primary tumor. New bilateral subpleural pulmonary nodules suggestive of metastasis. Figure 2 Due to progression, he restarts treatment with chemotherapy (palliative intention) with ERBITAX scheme (Paclitaxel 80 mg / m2 weekly (3 / 4s) + Cetuximab 400 mg / m2 followed by 250 mg / m2) with good tolerance,only highlighting secondary rash to cetuximab (predictive factor). After 3 cycles he presents significant partial response (Figure 3) and continues until 6 cycles. After 10 cycles it is considered whether to stop paclitaxel and follow on with cetuximab, but given the good tolerance they remain both of them. However, in January 2018, he presented a new pulmonary progression, so we decided to start a new strategy with inmunotherapy (Nivolumab), receiving 2 cycles to date.

Figure 2: PET-TC January 2017: locoregional tumor progression.

Figure 3: TC March 2017: Partial response of left adenopathy

Discussion

a. The concept of fragility is evaluated incorrectly through the Performance Status (PS). The ACE scale 27 assesses comorbidities and compares survival to having an advanced stage, so that is a fact to take into account more than the ECOG at the time of choosing the treatment.
b. When a patient progress to chemoradiotherapy, we have two good “palliative chemo” options: phase III EXTREME study(5-FU + Cisplatin + Cetuximab) or phase II of Hitt (Paclitaxel-Cetuximab) with fewer side effects, which is an alternative to cisplatin, achieving good response rates (20.43%) [1].
c. After 6 cycles of Paclitaxel + Cetuximab can be considered to keep Cetuximab as monotherapy, continue both or suspension until progression.
d. If pulmonary metastatic disease is controlled for> 1 year, we can consider surgical intervention.
e. Support treatment improves tolerance to chemotherapy. The indication of prophylactic enteral nutrition is a controversial issue, so we have to individualize.
f. We need predictive factors for each tumor type that we can know about before hand the prognosis and guide the treatment according to it. We must raise multidisciplinary strategies with the aim of achieving the best treatment sequence to improve survival in a population with few therapeutic options [2]

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Lupine Publishers | Micro-Environmental Systems and Endothelial Cells in Cooperative Tumorigenesis Account for Potential Malignant Transformation in Neurofibromatosis Type 1 Patients

Lupine Publishers | Open Acess Journal Of Oncology and Medicine

Abstract

Overall tumorigenesis in neurofibromatosis type 1 patients constitutes a series of specific targeting events with a central role enacted by proliferation of fibroblasts and endothelial cells in overproduction of growth factors and cytokines such as transforming growth factor-beta and CXCL12 cytokine. The plexiform neurofibroma well-illustrates dimensions of such cooperative participation within operative fields of the initial Schwann cell proliferation leading in a significant number of patients to malignant transformation of the peripheral nerve sheath tumors. Inclusive directions in operative targeting of Schwann cells or astrocytes are staged performance in the transformation of hyperproliferative induction and constitute further evolutionarily defined incorporation of such systems as endothelial cells. Hyperproliferative cell subsets are initial and also consequential target formulation of potential malignant states as induced in malignant peripheral nerve sheath tumors.

 

Introduction

Neurofibromatosis type 1 (NF1) is a neurogenetic disorder and involves both heterozygous and homozygous absence/reduction of neurofibromin that acts normally as a tumor suppressor. There is a need to assess predisposing genetic factors and loss of heterozygosity causing emergence of aggressive neoplasms in patients with NF1 [1]. The two hit hypothesis helps account for the emergence of Schwann cell-based proliferations and for neurofibromas and plexiform neurofibromas. Gherkin may act on tumorigenesis of cutaneous neurofibromas via growth hormone secretagogue receptor [2]. It is important to consider the neurofibroma that is based on micro-environmental potentiation of tumor generation in patients that develop malignant nerve sheath tumors and astrocytomas in patients with NF1 +/- genotype; this occurs in a manner that involves growth factor overactivity and mast cell and endothelial overactivity within a milieu that dysfunctionally stimulates tumorigenesis. Reactive oxygen species overproduction lead to epithelial-mesenchymal transit in patients with neurofibromin deficiency and plays a crucial role in NF1 tumor growth [3]. RAS activation alone is not sufficient for malignant transformation of peripheral nerve sheath tumors; signal transduction may potentially help identify therapies for this neoplasm type [4].

 

Neurofibromin

The dynamics of neurofibromin as a cytoplasmic protein involve the regulation of K-Ras, and the PI3K/Akt pathways; absence of neurofibromin leads to overactivation of these pathways in various ways in inducing tumorigenesis in such lesions as optic tract pilocytic astrocytomas, brain stem astrocytomas and also other CNS astrocytomas in terms of progression of these lesions. The cell of origin determines the temporal course of neurofibromatosis-1 low-grade glioma formation [5]. The micro-environment of plexiform neurofibromas of peripheral nerves and of nerve plexi include a 10% risk of malignant change with subsequent aggressive clinical behavior in the affected patients. Over expression of cellular retinoid acid binding protein 2 is reported in several cancer types, including malignant peripheral nerve sheath tumors (MPNSTs) [6].

Related Tumor Predispositions

The neurofibromin insufficiency status in Schwann cells and fibroblasts allows for enhanced participation of immune system component cells such as microglia as evidenced in optic pathway low-grade astrocytomas. Telomere erosion is described in many tumor types and may potentially drive genomic instability and clonal progression in NF1-associated MPNSTs [7]. Tumor dimensions include proliferation of astrocytic cells in optic pathways, and of various subtypes of stromal cells such as fibroblasts and mast cells in the peripheral nervous system. It is significant to consider particularly the micro-environmental active participation in the genesis of the most common tumor type in Neurofibromatosis type 1 patient, that is the neurofibroma, which invokes proliferation of fibroblasts and endothelial cells. The congenital plexiform neurofibroma is in fact a hypervascular lesion that transgresses tissue margins and induces a significant risk for malignant transformation. NF1 loss is the primary driver of tumorigenesis in neurofibromatosis type 1-related plexiform neurofibroma [8]. It is further to such considerations that important cooperative intervention in malignant transformation of plexiform neurofibromas invokes multi-type cells in inducing proliferation of an integral Schwann cell-fibroblastic twin population in enhancing potential malignant transformation of the peripheral nerve sheath. A therapeutic window for neuroprotective intervention exists as detected by optical coherence tomography in mice with optic glioma, and particularly as an accurate biomarker of retinal ganglion cell apoptosis [9]. The heterozygous absence of one neurofibromin allele in mice results in plexiform neurofibromas and low-grade optic pathway astrocytomas. Mast cells appear to play a causal role in neurofibroma formation and also in microglia in optic pathway glioma evolution [10]. Such implications of the micro-enviromental factors includes a distinctive cooperative participation that carries implications for significant enhancement of cell proliferation and of such cytokines such as transforming growth factor and CXCL12 in formulating malignant transformation in such tumors. The methylemetetrahydrofolate reductase 1298 and 677 gene polymorphisms are related to optic glioma and hamartoma risk in NF1 patients through effects on DNA synthesis and methylation [11].

Convergent Targeting

The related tuberous sclerosis complex is analogous to neurofibromatosis type 1 as a neurogenetic disorder associated with increased risk for astrocytomas in the form of subependymal giant cell astrocytomas. A convergent targeting of systems of cell proliferation include in particular cyclic AMP and Ras in a manner that includes dimensions of micro-environmental conditioning. Mutations of the NF 1 gene are frequent in many cancer types in patients without NF1 and this is suggestive of a more general role for the NF1 gene in oncogenesis. In melanoma NF1 mutations potentially drive tumorigensis and promote drug resistance [12]. Inclusive dynamics allow for permissive tumorigenesis in a manner that includes the incorporation of malignant transformation within confines of a Schwann cell-fibroblast-endothelial cell system in the case of malignant peripheral nerve sheath tumors. Astrocytes and microglia are analogous counterparts in the induction of CNS astrocytomas. Such considerations are inclusive phenomena of multi-component induction of potential malignancy that recharacterizes conditioning of the micro-environment of proliferative states preceding tumorigenesis. Interaction between neoplastic Schwann cells and their surrounding neural microenvironment has important implications for early cellular events promoting tumorigenesis in neurofibroma development [13].

Performance Dynamics

Performance dynamics of tumors in neurofibromatosis type 1 may potentially modify the biologic significance of a two-hit hypothesis in a manner that implicates micro-environmental conditioning of the resultant cell hyperplasias and proliferations in such lesions as peripheral nerve sheath tumors and astrocytomas. NF1 provides unique vantage points to examine co-contributions of molecular, cellular, and tissue processes in tumor biology [14]. Such proposed dimensions invoke in particular an over-activation in production and action of growth factors that provoke selective malignant transformation of hyper-proliferative lesions composed of Schwann cells and astrocytes in the peripheral and central nervous systems respectively. Plasma soluble levels of transforming growth factor-beta and interleukin-6 are increased in NF1 patients and a shift towards an anti0inflammatory profile has been reported in cells expressing cytokines [15].

Hyperproliferation

The hyperproliferative states affecting Schwann cells and astrocytes invoke also fibroblast and microglial cell proliferations in a manner transforming tumorigenesis. Such facilitation to tumorigenesis invokes dimensions of transformation as well seen in plexiform neurofibromas that may undergo malignant transformation in a significant number of affected individuals. Such considerations are selective targeting of specific cell subpopulations in a manner that allows permissive transformation. Insertional mutagenesis identifies a STAT3/Arid1b/beta-catenin pathway that drives neurofibroma initiation in the context of Nf1 loss [16]. Mast cells and fibroblasts may potentially incorporate endothelial cells that may participate as central dysregulatory dimensions in plexiform neurofibroma tumorigenesis. The provocations for malignant transformation further cooperate in systems of derivative consequence as hypervascular lesions that subsequently lead to potential malignant cells in individual patients. Cross species comparative oncogenomic may identify driver mutations in mouse cancer models and allow validation in human tumors [17].

Concluding Remarks

Propositional implications in tumorigenesis include the multi-component participation of Schwann cells on the one hand and of fibroblasts, mast cells, endothelial cells and also of microglia in an inductive process that includes specific pathways of malignant transformation. Endothelial cell proliferation is related to substantial participation in modes related to key-events of increased proliferation of Schwann cells and astrocytes in initial stages of lesion infliction. Inclusive phenomena have thus become systems of consequence in affecting such specific cell proliferative states. Such events occur within the added dimensions of directed targeting of multiple-agent micro environmental modeling of the initial proliferation of the Schwann cells or astrocytes. A pivotal series of roles played by fibroblasts, endothelial cells, mast cells and of microglia and astrocytes appears a dynamic milieu within added consequences of malignant transformation of both Schwann cells and astrocytes that progress as cooperative systems of tumorigenesis.

For more Lupine Publishers Open Access Journals Please visit our website:
http://lupinepublishers.us/
For more Open Access Journal of Oncology and Medicine Please Click Here:
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