The recent advances in functional genomics have discovered that a large number of long non-coding RNAs (lncRNAs) are pervasively transcribed from the human genome. Increasing evidence further indicates that lncRNAs are important for gene expression during cell differentiation and development through various mechanisms such as nuclear organization, post-transcription regulation, alternative splicing, and epigenetic regulation. Thus, aberrant expression of lncRNAs can cause abnormality in those cellular functions and lead to various pathological conditions. One of such fatal consequences is cancer metastasis which is responsible for more than 90% of cancer-related deaths. A good understanding of how lncRNAs regulate different genetic and epigenetic changes during different stages of cancer metastasis is important not only for general cancer biology but also for identifi cation of novel biomarkers and therapeutic targets for treatment of metastatic cancer. A significant progress has been made regarding the role of lncRNAs in cancer for past several years. In this study, we first discuss general functions of lncRNAs and then highlight recent fi ndings of how lncRNAs impact cancer metastasis, and finally we provide our perspectives on clinical implications of lncRNAs.

Notch pathway is a major determinant of cell fate, and research within the last 30 years has shown dysfunctions within this pathway in the majority of solid tumors and leukemias. The molecular mechanisms causing aberrant expression of Notch in cancer are still partially known. Mesotheliomas, breast, and cervical cancers are among the cancer types for which the dysregulation of Notch has been reported together with the association of simian virus 40 (SV40) or human papilloma virus (HPV) infections. In mesotheliomas and cervical cancer, there is clear evidence that these viruses cause and rely on dysregulation of the Notch pathway to promote and sustain cell transformation. The existence of a relationship in tumors between DNA viruses and Notch could have an impact on cancer therapy by implementing Notch inhibition to interfere with the growth of SV40- and HPV-positive cancers. In addition, since Notch links innate and acquired immunity and plays a key role in the regulation of the anti-viral response, targeting Notch in the presence of oncogenic viruses infections may help prevent the onset and progression of cancers associated with the exposure to these viruses.

Worldwide, colorectal cancer (CRC) is a leading cause of cancer death, primarily because of limited therapeutic options for those with advanced disease. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Besides its prominent role in bile acid synthesis, and lipoprotein and glucose metabolism, recent data indicate that FXR also plays a key role in regulating intestinal cell proliferation and carcinogenesis. Here, we review the role of FXR as a tumor suppressor in CRC, with particular emphasis on the molecular mechanisms underlying FXR-dependent tumorigenesis and its regulation, FXR-bile acid relationships and FXR-targeted drugs as potential therapeutic agents.

Aim: As our understanding of cancer stem cell (CSC) biology improves, search for inhibitory agents of CSCs and metastatic CSCs (mCSCs) positive for CXCR4 is warranted. Withaferin A (WA), a withanolide extracted from the medicinal plant Withania somnifera, has been shown to exhibit anti-cancer effects through multiple mechanisms. Whether WA could selectively target CSCs, mCSCs, or non-CSCs of a gastrointestinal (GI) carcinoma tumor remains unclear.

Methods: Side-population (SP) analysis, flow cytometric phenotyping and sorting, non-invasive imaging in conjunction with xenotransplantation, and immunohistology were used in this investigation.

Results: Using the lymph node metastatic GI cancer cell line UP-LN1, consisting of CD44high/CD24low floating (F) and CD44_low/CD24_high adherent (A) cell subsets, this study demonstrated that as compared with parental UP-LN1 cells or A cells, WA preferentially reduced F-cell proliferation, tumor sphere formation, and SP cells in vitro in greater effi ciencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/interleukin-6 axes, both of which are instrumental in the acquisition of metastatic ability. Attenuation of interferon-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with an anti-CXCR4 antibody, followed by Western blot analysis, showed signifi cantly reduced metastatic potential in vitro. The extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was signifi cantly greater than on the F cells without WA treatment, or F cells treated with control siRNA or with control IgG antibody. The observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse xenotransplantation.

Conclusion: WA could effi ciently block the formation of both CSCs and mCSCs in the UP-LN1 cell line, suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The most frequent sites of metastases are lungs, regional lymph nodes, adrenals and bones. However, an isolated sternal metastasis from HCC as an initial presentation has been rarely reported. A 45-year-old man presented with a progressively increasing mass over the anterior chest wall. On investigations, it was found to be arising from the sternum. Histopathology was suggestive of metastatic HCC, later confirmed by the presence of a 9 cm × 7 cm mass in the liver on abdominal computed tomography scan and a significantly elevated serum alpha fetoprotein level. Thus, metastasis from HCC should be included in the differential diagnosis of anterior chest wall mass and rapidly growing osseous metastases at unusual sites, even in the absence of signs of liver disease.

The myeloid extramedullary tumor is a solid tumor formed by infiltration of immature myeloid cells in various tissues of the body. This tumor is also identified as chloroma or myeloid sarcoma (MS). MS is a manifestation of acute myeloid leukemia (AML) occurring at presentation or during treatment or relapse. MS is associated with multiple chromosomal abnormalities and molecular mutations since patients with these disorders bear a high potential for MS manifestation. There is a high incidence of extramedullary infiltration (EMI) in AML. AML patients with EMI have a worse prognosis than patients without it. Hematopoietic stem cells and leukemic stem cells reside in a special bone marrow microenvironment called niche, which is essential for their normal functions. Cancers are exploited dysfunctional cell-cell and matrix-cell interactions, which convert a normal niche into a neoplastic niche. This study summarizes the current knowledge on the molecular and cellular characteristics of AML with EMI and extramedullary niches in AML patients.

Urinary bladder cancer (UBC) is a heterogeneous disease with highly variable clinical outcomes and responses to chemotherapy. Despite some advances in the molecular understanding of UBC, this knowledge still has not been translated to the clinic in terms of improvements in the prognosis and treatment of patients. Suitable urinary bladder tumor models representative of the human disease in terms of histology and behavior are needed to study factors involved in tumor initiation, progression and metastasis. Further, accurate model systems would facilitate identification of new therapeutic targets and predictive markers that could lead to optimization of existing therapies and development of new ones. Many established cancer cell lines derived from human urinary bladder tumors representing different grades and stages have been used as experimental models for UBC study. These cell lines reflect some of the genetic and morphologic alterations observed in human urothelial carcinoma and serve as simplified models to study the behavior of cancer cells in vitro. However, their translational potential is limited due to the artificial conditions, in which the cells are maintained, grown and tested. Animal models offer a more complex and realistic model for the establishment, development, and progression of tumors as well as to evaluate new therapeutic approaches. Over the years, the authors' group has worked with several UBC cell lines, established and characterized chemically induced UBC models, and patient-derived xenografts models. In this study, the authors will provide a summary of the UBC models developed by their group, analyze their translational potential and weaknesses, and define areas that remain to be explored.

Aim: The main aim of the present study was to evaluate the overall survival (OS) and time to treatment failure (TTF) in a cohort of relapsed/refractory diffuse large B-cell lymphomas (DLBCLs) not eligible for high-dose therapy (HDT) treated with gemcitabine in association with dexamethasone, cisplatin and rituximab (GDP-R) protocol. The secondary aim was to identify the prognostic factors impacting OS and TTF.

Methods: The authors retrospectively analyzed 45 patients with refractory/relapsed DLBCLs treated with GDP-R.

Results: Overall response rate (ORR) was 48.8%; complete response 15/45 (33.3%), partial response 7/45 (15.5%). Response was influenced by the number of previous therapies administered and International Prognostic Index (IPI) value. Although no significant impact occurred with regard to OS, patients pre-treated with 2 or < 2 chemotherapeutic regimens had better ORR (P = 0.014) and a longer TTF (P = 0.029 in multivariate Cox model). IPI value also influenced TTF. Patients with < 2 IPI value had significantly more prolonged TTF than the other ones (P = 0.048 in multivariate Cox model). Treatment was well-tolerated, with the majority of patients treated on out-patient modality. GDP-R regimen represents a valid treatment for aggressive relapsed/refractory B-cell lymphoma not eligible for HDT thanks to its efficacy and good toxic profile.

Conclusion: The number of previous chemotherapeutic regimens and IPI value select those who benefit more from this treatment.

Cancer-related fatigue (CRF) is a common polysymptomatic syndrome with no standard therapy. The authors present the case of a prostate cancer patient in whom, during hormone therapy, disabling CRF and urinary incontinence occurred. CRF was assessed according to the brief fatigue inventory (BFI). The patient received duloxetine, 60 mg daily, due to its impact on both CRF and incontinence. After 2 months, the BFI score decreased (from 9 to 2) and urinary incontinence resolved. After duloxetine discontinuation, the patient maintained a low BFI score. The authors conclude that, as a serotonin-noradrenaline reuptake inhibitor, duloxetine could be active on prostate CRF, especially with associated urinary symptoms. Therefore, a pilot placebo-controlled trial with duloxetine to treat prostate CRF may be worthwhile.

Cervical cancer is the most common malignancy in Indian women. It usually spreads locally or via regional lymphatics to retroperitoneal lymph nodes and hematogenous spread is rare. The occurrence of skeletal muscle metastases is a very rare event and only a few cases have been reported in literature. The authors present an unusual case of cervical carcinoma in a patient that presented with skeletal muscle metastasis 1 year after the treatment.

Modern brain tumor surgery stands in the pillar of maximum safe resection. Tumor borders are always challenging, especially infiltration zones in malignant brain tumors. Novel technologies are designed for a better delineation and to increase the extent of resection (EOR) in brain tumor surgery, such as: cortical and sub-cortical mapping strategies with somatosensory-evoked potentials, awake stimulation mapping and cortical/sub-cortical stimulation for motor pathways, important for resection in eloquent areas; intra-operative imaging as functional and intra-operative magnetic resonance imaging, diffusion tensor imaging and intra-operative ultrasound are important for the tumor borders and to achieve the gross total resection; neurochemical navigation methods as 5-aminolevulinic and sodium fluorescein are important for the non-contrast-enhanced tumor border; future methods can be achieved with augmented reality surgery, new intra-operative chemical markers, and visualization methods. Nevertheless all these techniques seem to be promising, the real challenge in the future will be held in how to apply them and how they really affect the prognosis of the patients. Also, new concepts in tumor genetics will provide knowledge for the tumor behavior and will guide resection. Despite all limitations, the increasing importance of safe EOR shows the possible benefits of the novel technologies and surgical advances in brain tumor surgery, taking it to a new step of the neuronavigation era.

The PI3K/AKT/mTOR (PAM) pathway is involved in a variety of cellular functions and often contributes to oncogenesis and cancer progression. It has been recognized that this pathway is frequently activated in the most common central nervous system cancers of adults and children, malignant gliomas and medulloblastomas (MB). In these tumors, the PAM network controls key functions necessary for cell invasion and metastasis, such as cell motility. This review summarizes the current knowledge about the role of PAM signaling in cell invasion and metastasis in gliomas and MB. Current approaches to inhibit cell invasion and metastasis by targeting the PAM pathway will also be discussed.

Brain infiltration by cancer cells is a complex process in which metastatic cells detached from the primary tumor must firstly survive in the blood flow, cross the blood brain barrier (BBB) and finally colonize a foreign microenvironment. The cells that successfully bypass the cellular barriers surrounding capillaries, proliferate to form micrometastasis and trigger the angiogenetic process. Different molecular mechanisms have been proposed to explain the metastatic behaviour of solid tumors that infiltrate brain tissue; in this review the most recent findings concerning mechanisms and genes potentially involved in brain metastasis, that differ according to primary tumor types, will be discussed. The three tumors that more frequently develop brain metastasis, lung cancer, breast cancer and melanoma, will be considered and, in addition, the role of BBB and the process of endothelial to mesenchymal transition in cancer metastasis will be briefly described.

Glioblastoma multiforme (GBM) is the most common and lethal brain tumor. Its prognosis remains very poor, despite the use of combined treatments such as surgical resection, radiation and chemotherapy. The major limitations for the treatment of GBM are its high invasiveness, tumor recurrence and resistance to treatments. Therefore, gene therapy appears as a relevant strategy for its treatment. Thus, we have investigated the use of growth-arrest-specific 1 (Gas1) for the treatment of GBM. Gas1 is a tumor suppressor protein that inhibits glioma growth by inducing arrest and apoptosis of tumor cells. Moreover, we have shown that a soluble form of Gas1 acting in both autocrine and paracrine manners is also effective inhibiting tumor growth in animal models, indicating its potential as an adjuvant for the treatment of GBM.

Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

While secondary solid cancer into the eye orbit is rare, it is the most common site for primary metastasis in female breast cancer. We report a case of a sixty-six years old woman presenting to her optician with complaints of double vision. Magnetic resonance imaging revealed an invasive lesion in the superior and medial rectus muscles of the right orbit, biopsy of which confirmed this as an infiltrating breast carcinoma. Investigation of the primary lesion showed an advanced invasive ductal carcinoma of the right breast. She was then treated with radiotherapy to the orbit and a non steroidal aromatase inhibitor Anastrozol (Arimidex®). We herein review and discuss the literature, epidemiology, mechanism of tumor spread, the “seed and soil” theory, clinical presentation, pathology, and management of this uncommon presentation.

Neuroendocrine tumors of the oral cavity and jaws are exceedingly rare. They include paragangliomas, a melanotic neuroectodermal tumor of infants, small cell carcinomas, and Merckel cell carcinomas. Most have been non-functional in nature. Breast, lung, liver, colon, and prostate are the most common reported primary malignancies which can metastasize to the oral cavity. In most cases, oral metastases involve maxilla and mandible rather than soft tissues. The premolar-molar region is the most common localization. The purpose of this article is to describe a rare case of a high grade neuroendocrine tumor of the mandible which metastasized from the cervix.

Renal cell carcinoma (RCC) is well known for its metastatic potential and predilection for unusual sites of metastasis. Metastasis to the bladder is rare and has been reported predominantly from clear cell RCC. We report a case of a 72-year-old male presenting with a bladder tumor which on histopathological evaluation was found to be a metastasis from papillary RCC, 7 years after radical nephrectomy. This case highlights the need to maintain a high index of suspicion to diagnose bladder metastasis in a patient with a history of RCC presenting with a bladder lesion.

Aim: To evaluate the diagnostic value of technetium Tc99m-tetrofosmin (^99mTc-TF) in primary cancers of the head and neck. Methods: Methods: Single photon emission computer tomography with planar imaging of the neck for primary site evaluation and whole body scanning for assessment of metastases in 12 patients with newly diagnosed head and neck cancer. Tumor-to-background index (T/Bg) was derived in patients with positive findings (tumor or lymph nodes). Results: The tomographic images showed increased tracer uptake in pathological sites (primary tumor or lymph node) in 9 patients (overall sensitivity 75%). Primary tumor was visualised in 7 patients (sensitivity 58%) and infiltrated lymph nodes in 4 out 7 patients (sensitivity 57%). Mean values for T/Bg index were 5.44 ± 1.28 for primary tumor and 4.25 ± 1.67 for lymph nodes. Mean values for T/Bg index were 4.5 ± 0.71 for patients with in situ and grade I carcinoma and 6.68 ± 0.36 for patients with tumor grade II and III (P = 0.034, Mann-Whitney U test). Conclusion: The present study demonstrates that ^99mTc-TF is a valuable radiotracer for head and neck cancer imaging. To determine the potential role of this imaging protocol in clinical practice will require a larger sample size.

Aim: This study was performed to assess the extent of interfraction uterine motion during radiotherapy for cervical cancer and uterine body carcinoma while maintaining a strict bladder filling protocol. Methods: Twenty-four patients with cervical cancer or uterine body carcinoma who were treated on a linear accelerator, were recruited. During the course of external beam radiotherapy, cone beam computed tomographic scans were taken, once at the start of treatment and then weekly until the completion of the radiotherapy course. Patients were instructed to maintain a strict bladder filling protocol. After negating the effect of patient’s setup error by offline cone beam computed tomographic imaging, the position of the uterus was defined in the clinical target volume. Then the position of the uterus was compared in the following weekly scans. The position of the uterus was also correlated with the position and the filling of the bladder. This change in uterus position was measured separately in the anterioposterior (AP), superioinferior (SI), and lateral directions. Results: According to calculations based on weekly imaging, The mean values of shift in AP, SI, and lateral directions were respectively 0.67, 0.29, and 0.23 The mean extent of motion in the uterine position on a daily basis for individual patients ranged from -2.28 to +1.3 in AP, -0.56 to +0.71 in SI, and from -0.6 to +0.45 in lateral directions. Conclusion: At least once a week cone beam computed tomography might be necessary to minimize the geometrical miss and deliver the planned doses to the target tissue and normal structure provide best results with minimum toxicity by maintaining a bladder volume of about 100 mL and an empty rectum during the whole course of treatment. The daily anatomical shift and contour of the patients maintaining a bladder volume of approximately 100 mL with an empty rectum may result in asymmetrical conforming to the planning target volume and hence appropriate and adequate planning target volume margins are required.

Primary malignant melanoma of the central nervous system is rare, and the events involving the spinal cord are even more infrequent. A 30-year-old male presented with a mass lesion of the spinal cord. After radiological workup, the mass was resected in December 2012. The histopathological examination report and immunohistochemistry suggested malignant melanoma. PET-CT scan, brain MRI, and funduscopic examination did not reveal malignant melanoma elsewhere in the body. The patient received postoperative radiotherapy until March 2013. Presently, the patient is asymptomatic with normal neurological functions.

Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system (CNS) tumors and greatly influence mortality and therapy-induced long-term morbidity in survivors. A number of in vitro and ex vivo assay systems have been established to better understand the infiltration and metastatic processes, to search for molecules that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness. These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled environments. However, the urgent need for novel anti-metastatic therapies has provided an incentive for the further development of not only classical in vitro methods but also of novel, physiologically more relevant assay systems including organotypic brain slice culture. In this review, using publicly available peer-reviewed primary research and review articles, we provide an overview of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors. Furthermore, we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be integrated to improve current research methods for metastatic brain tumors. We believe that such rationally improved methods will ultimately increase our understanding of the biology of brain tumors and facilitate the development of more efficacious anti-metastatic treatments.

The incidence of metastatic disease in the central nervous system (CNS) is rising. According to current estimates, up to a third of adult cancer patients will suffer from CNS metastasis. Clinical evidence-based data from prospective randomized trials are rare, however, because CNS metastasis patients were often excluded from clinical trial participation. The management of CNS metastasis patients is therefore rather ill-defined and an interdisciplinary challenge. Recent basic and translational science data have begun contributing to a more profound understanding of the molecular mechanisms leading to invasion of tumor cells into the CNS. This report reviews advances, challenges, and perspectives in this field.

Central nervous system (CNS) cancer is a devastating illness with unmet therapeutic needs. Establishing biomarkers that have the potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great interest. Cerebrospinal fluid (CSF) has been extensively targeted for the detection of molecules that might be useful markers for cancer detection. However, so far very few of such markers have found a standardized routine clinical application. This review examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS tumors.

Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m² weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m²/5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.

Due to the lack of effective treatments, advanced colorectal cancer (CRC) remains a leading cause of cancer death in the United States. Emerging evidence supports the observation that muscarinic receptor (MR) signaling plays a critical role in growth and progression of CRC. MR activation by acetylcholine and bile acids results in transactivation of epidermal growth factor receptors (EGFR) and post-EGFR signal transduction that enhances cell proliferation, migration, and invasion. Here, the authors review recent progress in understanding the molecular mechanisms underlying MR-mediated CRC progression and its therapeutic implications.

The importance of human papillomavirus (HPV) infection and its role in the progress of cancer have been widely evaluated. The understanding of HPV association with certain cancers, such as cervical cancer, is very well established. A big step forward in the prevention of HPV associated cancers with the use of early detection by screening strategies has also been taken. In the last decade, development of HPV vaccination has reduced the number of cases in HPV infections and infection induced cancers. In this report, we review the HPV pathogenesis and highlight the mechanism of HPV involvement in cancer development.

Lung cancer is one of the most common and deadliest forms of cancer. It accounts for 13% of all new cancer cases and 19% of cancer-related deaths. In India, lung cancer constitutes 6.9% of all new cancer cases and 9.3% of all cancer cases. There has also been a dramatic rise worldwide in both the absolute and relative frequencies of lung cancer occurrence. In 1953 it became the most common cause of cancer mortality in men. By 1985, it became the leading cause of cancer deaths in women, causing almost twice as many deaths as breast cancer. The demographic profile of lung cancer has changed greatly over the years; however, methods for diagnosing, screening, and managing lung cancer patients have improved. This is due to our growing understanding of the biology of lung cancer. It is now possible to further define lung cancer types beyond small cell lung carcinoma and non-small cell lung carcinoma. Moreover, new histology-based therapeutic modalities have been developed, and more new lung cancer biomarkers have been uncovered. Therefore, more detailed histological characterization of lung cancer samples is warranted in order to determine the best course of treatment for specific patients. This review article describes how these new molecular technologies are shaping the way lung cancer can be treated in future.

The first case of osteonecrosis of the jaw (ONJ) related to azacitidine therapy was reported. A 64-year-old male with acute myeloid leukemia, who received 5-azacitidine, presented with pain and purulence of the right second premolar. An unsuccessful endodontic therapy resulted in dental extraction 6 months later. The post-extraction non-healing socket was managed with antibiotics and multiple surgical debridements without response. ONJ stage 2 was diagnosed 12 months after the initial symptoms of pain and purulence and was managed conservatively. Currently the patient is still receiving 5-azacitidine therapy, while ONJ remains asymptomatic. This case highlights the presence of alveolar bone disease prior to the appearance of ONJ. Osteonecrosis in chemotherapy, although rare, may increase as long-term survival of cancer patients, who receive those medications increases. Health care professionals need to be alert, while collaboration with an experienced oral/dental oncologist would be beneficial to the patient.

Intracystic (encapsulated) papillary carcinoma of breast is a rare variant of breast cancer. It is usually a low-grade tumor showing estrogen, progesterone positivity. The authors report an unusual case of intracystic papillary carcinoma showing high nuclear grade, brisk mitosis, and necrosis with triple negativity for estrogen, progesterone, and Her-2/neu receptors, as well as negative axillary lymph nodes. Such cases need to be reported to increase awareness so that they will be managed conservatively, avoiding any overtreatment despite being high grade and triple negative.

Skeletal metastasis in carcinoma cervix occurs in about 0.8-23% of cases. These lesions are usually radiographically lytic. Very few cases of metastases to the skull have been identified, about 5 cases to the best of our knowledge. We present a case of adenosquamous cell carcinoma of cervix with fat attenuating skull metastases in a 38-year-old lady that is not reported till date. The lesion was lytic, expansile and with negative attenuation of -15 to -30 Hounsfield units corresponding to fat.Metastases must be included in the differentials of scalp lesions. A history of recent onset of swelling and associated lytic areas in calvarium on contrast enhanced computed tomography with multiplicity can give a clue to metastatic nature of disease.

The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

Long-term quiescence or dormancy is a fundamental feature of cancer stem cells (CSCs) that are genetically identical to the malignant clone but constitute the only cells with tumor propagation potential within the overall tumor population. These quiescent cells show significant resistance to radiation and antiproliferative chemotherapy due to distinctive properties that seem to be related to their stem cell-like character. Hence, successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also the CSCs. Using serum-starved KG1a cell line as an experimental model system of quiescent leukemic cells (QLCs), the present study demonstrates that QLCs exposed to low concentrations of curcumin show high proliferative potential. Furthermore, when subjected to a combination therapy consisting of low concentrations of curcumin and 5-fluorouracil (5-FU), the QLCs displayed a high kill with an increase in the levels of nitric oxide (NO) and reactive oxygen species. These results were further consolidated with the observation of high caspase-3 activity in cells subjected to the combination therapy. This may suggest that low concentrations of curcumin stimulate the QLCs to become mitotically active, thereby sensitizing them to killing by the antimitotic drug, 5-FU.

Lung cancer is the leading cause of cancer-related death worldwide. Advances in molecular biology have unveiled various targetable mutations with epidermal growth factor receptor (EGFR) being most common. EGFR testing is recommended for all locally advanced or metastatic adenocarcinoma lungs but recommendation in squamous histology is uncertain. However, just on the basis of histology, EGFR testing should not be withheld in patients diagnosed as squamous cell cancer on small biopsy, in females, never smokers and Asians. We report two cases with squamous cell lung cancer diagnosed on small biopsy, in non smoker females with EGFR mutations emphasizing the importance of testing in such population.

Acrospiromas are cutaneous tumors of sweat duct differentiation. Although various eccrine sweat gland tumours including benign acrospiroma are widely reviewed, malignant acrospiroma is rarely reported. Clinically, they resemble other cutaneous lesions and the primary treatment is wide local excision with or without lymph node dissection. The efficacy of adjuvant chemotherapy and radiation therapy requires further investigation.

Aim: Esophageal cancer is one of the major types of cancers, causing death of approximately 5% of all cancer deaths. This is due, in large part, to both relatively ineffectual and unavailable treatment. In order to develop an effective treatment strategy against esophageal cancer, it is important to target metastatic genes. In the present study, we have used a cancer-associated fibroblast (CAF) cell line derived from culturing peripheral blood mononuclear cells from a metastatic esophageal cancer patient to see whether chitosan nanoparticles (Ch-Np) treatment can modulate the metastatic phenotype of CAF cells by using various cellular and molecular markers.

Methods: A CAF cell line was developed from peripheral blood mononuclear cells (PBMC) from a metastatic esophageal cancer patient. The cells were treated with 100 µg/mL of chitosan nanoparticle in vitro for the morphological and oncogenic characteristic studies, along with the expression of various genes involved in process of tumor development and metastasis. Techniques such as Light and Phase Contrast Microscopy, cell growth rate, Scratch metastatic assay, and molecular profiling were carried out to see changes in CAF cells before and after Ch-Np treatment.

Results: It was observed that CAF cells grew in monolayer and had a doubling time of 25 ± 0.38 h. Morphologically, the cells had a fibroblastic appearance. After treatment with 100 µg/mL of Ch-Np in vitro, there was an increased doubling time to 30 ± 0.83 h. Similarly, Scratch Assay showed an inhibition in the metastatic property of these cells. These findings were confirmed with gene expression studies. It was also observed that there was complete down-regulation of metastatic genes MMP1 and MMP9 and chemokines such as CXCR-4, CXCR-7, CCR-5, and SDF-1, indicating that Ch-Np inhibited the metastatic characteristic of CAF cells.

Conclusion: This study has shown that there was an inhibition of metastatic properties of CAF cells after treatment with Ch-Np, suggesting that Ch-Np can be a delivery system used for targeting cancer cells for treatment of esophageal cancer.

Aim: The aim of the study is to investigate the impact of the cytochrome P450 2E1, which is the most efficient CYP450 family member in generating reactive oxygen species (ROS), on cellular energy metabolism of breast cancer cells and therefore the effects of CYP2E1 on breast carcinogenesis. Methods: The estrogen receptor positive MCF-7 and the triple negative MDA-MB-231 breast cancer cells were used as experimental system to estimate ROS generation in these cells overexpressing CYP2E1 and treated with the glycolytic inhibitors 3-bromopyruvate or 2-deoxyglucose in the presence or absence of the CYP2E1 inhibitor chlormethiazole. Adenosine triphosphate (ATP) assay was used to measure ATP production and lactate assay to quantify the efflux of lactic acid in breast cancer cells treated with the CYP2E1 inhibitor chlormethiazole, the mitochondrial membrane potential and cell viability assays were employed to assess the pathway of cellular energy production and cellular death respectively after treatment of MCF-7 and MDA-MB-231 with the CYP2E1 activator acetaminophen or the CYP2E1 inhibitor chlormethiazole. Results: The results indicated increased ROS generation in breast cancer cells overexpressing CYP2E1. ROS generation was differentially regulated in breast cancer cells upon treatment with the CYP2E1 inhibitor chlormethiazole. Chlormethiazole treated MCF-7 cells exhibited reduced lactate efflux implying that CYP2E1 directly or indirectly regulates the glycolytic rate in these cells. Furthermore the mitochondrial membrane potential of both MCF-7 and MDA-MB-231 cells was differentially affected by the CYP2E1 activator acetaminophen versus the CYP2E1 inhibitor chlormethiazole providing additional support for the involvement of CYP2E1 in energy metabolic pathways in breast cancer. Conclusion: Results presented in this study provide evidence to suggest that CYP2E1 regulates cellular energy metabolism of breast cancer cells in a manner dependent on cell type and potentially on the clinical staging of the disease therefore CYP2E1 is a possible breast cancer biomarker.

Neuroendocrine tumors (NETs) encompass a broad spectrum of malignancies all derived from neuroendocrine cell lineage, affecting many different organs including the gastrointestinal (GI) tract, the endocrine pancreas, the thyroid, the skin and the respiratory tract. These tumors as a group are very heterogeneous, with varying characteristics attributed to each tissue of origin and tumor subtype. The pathogenesis of the different subtypes of NETs is not fully understood, but recent studies suggest the Notch signaling pathway may be dysregulated in these tumors either by under or overexpression of Notch receptors and/or ligands, or by disruption of pathway functionality through other means. Notch receptors can function as tumor suppressors in some cellular contexts and oncogenes in others which may, in part, account for the wide range of phenotypes present in NETs. Cancer stem cells are present in these tumors and may be responsible for the high rate of chemotherapy resistance, recurrence and metastasis. The heterogeneity of NETs suggests that to fully understand the role of Notch signaling and the therapeutic implications thereof, a comprehensive and systematic analysis of Notch expression and function across all NET subtypes is required. Here we outline the current knowledge base with respect to current therapies and Notch signaling in neuroendocrine tumors of the lung, skin, thyroid, GI tract and endocrine pancreas.

In neuroendocrine tumors (NETs), liver metastases (LM) represent the most crucial prognostic factor, irrespective of the primary tumor site. At diagnosis, about 65-95% of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) show hepatic metastasis. Management strategies of LM are heterogeneous and range from systemic therapy to liver-directed procedures. The type of systemic therapy used is dependent on the grade and proliferation of the tumor and includes somatostatin analogues, interferon, m-Tor and tyrosine kinase inhibitors, and chemotherapy. Angiographic liver-directed techniques, such as transarterial embolization/chemoembolization and selective internal radiation therapy, offer excellent palliation for patients with liver-predominant disease. In highly selected cases, liver transplantation and peptide receptor radionuclide therapy are considered. The relatively low disease incidence and the diversity of presentation have led to a lack of well-conducted randomized controlled trials comparing the efficacy of different treatment options. Experience indicates that surgery is the only treatment that offers potential for cure. For unresectable lesions, the absence of data from rigorous trials limits the validity of many publications that detail management. In this review we will discuss the existing approaches for hepatic metastases from GEP-NETs.

Gastroenteropancreatic neuroendocrine tumors (NETs) have an incidence of 2.39 per 100,000 inhabitants per year, and a prevalence of 35 cases per 100,000 inhabitants; the gap between these rates is due to the relatively long survival time of these tumors, which can be thus considered as chronic oncological diseases. Recently, more therapeutic options have become available, but criteria for defining timing, priority and sequence of different therapeutic options are still debated. This review offers an overview of pancreatic and small bowel NETs, critically underlining the issues that still need to be clarified and some controversial issues on the therapeutic approach for NET patients.

Merkel cell carcinoma (MCC), first described in 1972, is an aggressive primary cutaneous carcinoma able to incorporate both epithelial and neuroendocrine features. MCC mainly appears in individuals in their eighth decade and it is related to a high mortality rate. The etiology of this rare disease is not well-understood but ultraviolet radiation exposure, immune suppression, and aging have a consistent role in its pathogenesis. Usually, clinical lesions appear as asymptomatic coloured dermal nodules. The tumour can involve lymph nodes but further evaluation with imaging is recommended. The common approach for localized disease is surgical. This work reports a case of an 86-year-old man with locally advanced MCC where, based on clinical experience, oral mono-chemotherapy with single-agent etoposide was chosen as first-line therapy. A complete objective response was achieved in 2 months.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumours often producing high levels of hormones and causing symptoms. There are a number of different types of NENs. They usually arise as advanced and low/intermediate grade only in a minority of cases, as high grade. Treatment depends on which type and may include surgery, interventional radiology, and systemic treatment, including chemotherapy, somatostatin analogs, interferon α2b, peptide receptor radionuclide therapy, and only for pancreatic neuroendocrine tumors, molecular targeted agents, including everolimus and sunitinib. The aim of the article is to review the medical approaches with somatostatin analogs and chemotherapy. The treatment of NENs is mainly based on their biological characteristics of aggressiveness and functional features, such as symptoms and endocrine markers.

⁶⁸Ga-DOTA-peptide PET/CT is a recommended imaging modality in the workup of neuroendocrine neoplasms (NENs), which shows high diagnostic sensitivity and is a strong predictor of successful somatostatin receptor directed treatments. Although not routinely recommended, reliable evidences show that ¹⁸F-FDG PET/CT can provide complementary information in this setting with the ability to discriminate slow-proliferating tumors from aggressive, rapidly-proliferating tumors. Further, it has been proposed as an independent prognostic factor for the prediction of either overall survival or progression free survival. In this review, we provide insight into the biologic significance of ⁶⁸Ga-DOTA-peptides and ¹⁸F-FDG uptake, and of the use of double tracer (⁶⁸Ga-DOTA-peptides plus ¹⁸F-FDG) PET/CT in the clinical evaluation of patients affected by NENs.

Neuroendocrine tumors (NETs) represent a spectrum of rare neoplasms arising in different organism sites. Depending on the site of onset, they also can be distinguished using lab exams (secreting vs. nonsecreting), clinical symptoms (functioning vs. nonfunctioning), behavioral, morphological characteristics (tumor cells’ architectural growth patterns, mitotic and Ki-67 index, presence of necrosis), and grade of cellular differentiation. The aim of this review is to focus on the main signaling pathways targeted by medical treatments of advanced sporadic gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) neuroendocrine neoplasms. The scientific literature regarding treatment of advanced GEP and BP-NETs has been extensively reviewed using MEDLINE and PubMed databases, selecting principal and more recent research articles, clinical trials, and updated guidelines. Somatostatin analogues represent a valid approach to control symptoms in functioning tumors and to inhibit tumor progression in certain categories on the basis of the typical somatostatin receptor expression observed in NETs. The pathogenesis of NETs has been the subject of increased interest in recent years. Many driver mutations pathway genes have been identified as important factors in the carcinogenesis process and, therefore, as potential targets for new anticancer therapies. Activating mutations have been shown in epidermal growth factor receptor, stem cell factor receptor, platelet-derived growth factor receptor, vascular endothelial growth factor, basic-fibroblastic growth factor, transforming growth factor, insulin-like growth factor-1, and their receptors. Effective M-Tor inhibition pathway modulation has led to the approval of drugs in this field such as everolimus. New drugs and several combination regimens with targeted and newer biological agents are being developed and tested in recently conducted and ongoing trials.

Neuroendocrine tumors are rare neoplasms arising primarily in the gastrointestinal tract and lung. The liver is the most common site of metastases, but these tumors can rarely metastasize to atypical sites. Surgery is the only curative approach while the optimal medical treatment is debated. From this perspective, a multidisciplinary approach for each single case becomes very important. In this report we describe the case of a male affected by a single intraorbital metastasis from a midgut well differentiated neuroendocrine tumor. The patient refused surgical removal and therefore he was at first treated with stereotactic radiotherapy and systemic treatment with a somatostatin analog (SSA). After achieving a stable disease for four months he underwent primary tumor resection. Six years after the initial diagnosis, the patient is currently stable and receiving SSA at standard dose.

Pancreatic neuroendocrine tumors (pNETs) can be associated with different clinical syndromes. Insulinoma is the most common functioning pNET characterized by hypoglycemia and hyperinsulinemia. The authors report a case of a man presenting with hypoglycemia and biochemical features of insulinoma. A pancreatic lesion was found and growth hormone (GH) deficiency was also diagnosed associated with an empty sella present on the pituitary magnetic resonance imaging. The disappearance of hypoglycemia and normalization of GH secretion after surgical resection of the pancreatic lesion, revealed a rare pNET secreting insulin-like growth factor II.

Neuroendocrine neoplasms (NETs) are rare tumors that are increasing in incidence. NETs are characterized by heterogeneous biological behaviour, clinical presentation and course. A sensitive and specific diagnostic and prognostic circulating biomarker useful for all sites, grading and staging of neuroendocrine tumors is still an unmet need. The aim of this article was to review current neuroendocrine and oncologic scientific society guidelines and position statements, and propose recommendations for the most frequent clinical practice queries on circulating neuroendocrine tumors biomarkers. The authors searched for NCCN, NANETS, ESMO, ENETS, UKINETS, AME management guidelines or position statements available from PubMed up to 7th January 2016. From these results we chose guidelines or position statements published by scientific societies or institutions in USA, Europe and Italy with recognized expertise in neuroendocrine tumor patient management. The authors present suggestions for clinical practice based on this analysis.

Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment.

Peritoneal Carcinomatosis (PC) from metastasization of Gastric Cancer (GC), either present at first diagnosis of GC or as recurrence, is considered a fatal disease with no hope of definitive cure. Although newer agents like S1 and docetaxel have shown some promise, the median overall survival with the current first line chemotherapy is only 8 to 14 months, and is not greatly improved by adding targeted therapy. A multi-modal approach with cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed along the last two decades in order to tackle this problem. It’s an aggressive, combined treatment still under investigation. Studies coming from Europe and Far East reported long-term survival with 5-year survival rates up to nearly 25% in case of complete cytoreduction. Prophylactic/adjuvant setting is the most evidence-based indication for HIPEC in advanced-stage GC patients without PC, in order to prevent peritoneal recurrence and to improve overall survival. The rationale for immuno treatment in patients with gastric PC is strong. A randomized phase II study, combining complete CRS with intraperitoneal catumaxomab is on-going. The detection of free peritoneal cancer cells is the more realistic and practical way for the identification of patients at risk of carcinomatosis after surgery. The routine use of techniques of molecular detection in peritoneal washing appears to be the more sensitive method. Such patients are potential candidate for multimodal and locoregional treatments in order to prevent the peritoneal recurrence.

Gliomatosis cerebri (GC) is an uncommon disease, defined as diffuse infiltration of neoplastic glial cells involving at least three cerebral lobes. GCs in young population are rare. We described a case of 14-year-old woman with GC who did not receive any recommended treatment, because the patient’s family refused. The patient had a rapid deterioration in 5 months after first symptoms due to intratumoral bleeding. This is the first case report of intratumoral bleeding after diagnosis of GC is made, resulting in poor outcome. GC may acquire possibility of intratumoral hemorrhage through its development.

Aim: The aim of this study was to evaluate the efficacy of treatment related to age in metastatic non-small cell lung cancer (NSCLC). We compared young and elders (> 70) in the setting of a regional Spanish hospital. We hypothesized that elder benefit as much as younger patients from chemotherapy in stage IV NSCLC. The study was limited to performance status 0-2.

Methods: Clinical and demographic characteristics were reviewed form medical records. Type of treatment was collected and compared, as well as benefit from treatment, in terms of overall survival.

Results: 322 patients (162 young, 160 aged) Elderly patients received less active treatment (63% vs. 86%, P = 0.001). Elderly received less chemotherapy, less cisplatin-doublets, more carboplatin-combinations and monotherapy (P = 0.035). The benefits of treatment were similar, regardless of age. Smoking status demonstrated a prognosis impact for elder patients treated with chemotherapy. Those who remained active smokers had a lower overall survival in the aged group. In a multivariate analysis, the Eastern Cooperative Oncology Group, active treatment and non-smoking history were favorable prognostic factors for elder patients. Smoking had not impact on young patients.

Conclusion: Elderly patients were undertreated in clinical practice. Treatment showed similar overall survival despite of age. The impact of smoking seems to be more significant in the elderly population.

The authors present a case of histologically benign and incidentally discovered millimetric solitary fibrous tumor of the bladder, invisible to radiologic imaging and clinically benign. The case came to our attention because of repeated episodes of renal colic. As opposed to the present case, solitary fibrous tumor are generally discovered when they reach certain dimensions, being slow-growing, painless masses. Such a tumor of the bladder is a very rare finding, with less than 20 cases reported, and it has yet to be described with such a small size. The main differential diagnoses are discussed. Such tumors with histological features of malignancy are also described in the literature. However, the present case had a bland appearance so a conservative approach with an excision was adopted. No signs of recurrence are present at follow-up.

Primary carcinoma of breast is common but breast is a rare site of metastasis and metastases from extramammary sites are even rarer. Metastasis to breast from rectal carcinoma is very unusual and till now 19 cases of breast secondaries from colorectal carcinoma have been reported in literature which include 14 cases where the primary site was colon and remaining 5 were from the rectum. Here the authors report a case of adenocarcinoma anorectum who had completed treatment and after 4 months developed a lump in her left breast which was metastatic. Metastatic lesions of breast are usually part of a widely disseminated disease but this case presented as a solitary breast metastasis which mimicked as second primary cancer of the breast.

Aim: Tyrosine kinase inhibitors are part of the armamentarium to treat metastatic renal cell carcinomas (mRCC). Costa Rica has approved sunitinib in the first line setting. The authors conducted a retrospective study to address the effectiveness and safety profile of sunitinib in our population in terms of overall survival (OS) and progression free survival (PFS).

Methods: The authors analyzed all patients who were treated with sunitinib diagnosed with mRCC in the three National Hospitals (Hospital Mexico, Hospital San Juan de Dios, and Hospital Calderon Guardia) from February 2007 to June 2015. Demographics, safety profile, and efficacy (OS and PFS) were obtained from medical records. OS and PFS were calculated using the Kaplan Meier method and a Cox Proportional Model Analysis was used when OS and PFS were compared in subset of patients.

Results: Seventy-seven patients were included; mean age was 58.9 years. Fifty-four patients were male (70.1%). The most common histologic type was clear cell carcinoma (87%), followed by papillary (9.1%) and chromophobe (2.0%) types. Median OS was 21.0 months [95% confidence interval (CI): 13.42-28.58]. Median PFS was 13.7 months (95% CI: 11.24-16.16). Patients aged 65 years or older experienced worse PFS and OS than younger patients (median PFS: 8.2 vs. 17.6 months; P = 0.011) (median OS: 19.0 vs. 29.0 months; P = 0.022). Sunitinib was well tolerated and no serious side effects were reported.

Conclusion: This is the first study in Central America showing that sunitinib, first line, in mRCC is as effective as reported in pivotal clinical trials and expanded use studies in terms of PFS and OS.

Spontaneous metastatic clostridial myonecrosis is a rare condition caused by Clostridium septicum. The underlying lesion is usually either a colonic neoplasm or leukemia. The authors reported a 67-year-old female who presented with acute abdomen secondary to a perforated sigmoid cancer and who developed gas gangrene in her right leg. Unfortunately, despite all resuscitative measures, she died. The authors reviewed the literature; the diagnosis of metastatic myonecrosis was based on a high index of suspicion, development of bullae containing gram-positive rods, and subcutaneous crepitus (although this was a late sign). Treatment involves aggressive fluid replacement, high doses of intravenous penicillin, high concentration of oxygen, and surgical debridement, and/or amputation. The mortality remains very high, despite all the above measures.

Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.

Aim: The present study sought to discover the role of Nibrin protein in 100 patients with oral squamous cell carcinoma (OSCC) and its potential relationship with clinicopathological parameters.

Methods: Nibrin expression was evaluated immunohistochemically using the modified H-score method.

Results: The present study included 20% of patients with stage I disease, 22% of patients with stage II disease, 18% of patients with stage III disease, and 40% of patients with stage IV disease. Nibrin showed a significant positive correlation with moderately/poorly differentiated tumor tissues (P = 0.028), while significant inverse correlation of Nibrin expression was observed with tumor size (P = 0.018) and tumor stage (P = 0.039). Further, using univariate survival analysis it was observed that strong Nibrin expression was significantly associated with disease relapse in early stage OSCC patients (P = 0.049).

Conclusion: Thus, the present study revealed that Nibrin could be used as a prognostic marker in patients with early stage OSCC.

Solid organ transplant recipients are at increased risk of developing malignancies, even decades after transplant, due to the prolonged use of immunosuppressant drugs. A 35-year-old male underwent renal transplant for end stage renal disease 18 years previously and was on immunosuppressive drugs since that time and was on regular follow up. In 2016, he developed a squamous cell carcinoma of tongue, which was operated and adjuvant radiation therapy was given. The patient is currently on follow up and asymptomatic. Though squamous cell carcinoma of tongue is a relatively common malignancy in the general population, it is very rare in transplant recipients. Hence, such patients require longer follow-up, active surveillance, and screening for early diagnosis and prompt treatment of premalignant and malignant conditions.

Despite the fact that the majority of cancer patients succumb to metastatic disease, most aspects of tumor metastasis are not understood in detail at present. Cell biologic steps of dissemination are difficult to characterize in human tumors and research is in large part confined to cell line and experimental animal studies. Epithelial-mesenchymal transition (EMT), intravasation of malignant cells, dissemination as circulating tumor cells (CTCs) and eventually mesenchymal-epithelial transition (MET) at distal sites are steps believed to be involved in metastasis. Small cell lung cancer (SCLC) is distinguished by early dissemination and excessive numbers of CTCs, which allowed for the ex vivo expansion of six permanent CTC lines taken from relapsed patients. Cells exhibit an epithelial phenotype with partial EMT traits and are chemoresistant due to formation of large tumorospheres. Since cells may have invaded without undergoing EMT, the role of MET is uncertain. These SCLC CTC cell lines seem to represent the metastasis-inducing cancer cells; these are the minute subpopulation of CTCs capable of surviving in the circulation and transitioning to metastases, leading in turn to resistance and failure of therapy. Full characterization of these lines is expected to provide the markers to find the relevant CTCs among the highly heterogeneous population observable in the context of tumor recurrence.

Primary malignant circulating prostate cells (CPCs) are those detected in blood before definitive treatment for prostate cancer. CPCs can be detected in men with benign prostate disease; however, some methods to distinguish between benign and malignant prostate cells have to be validated. This study presents a review of the subject, including theoretical considerations for the selection of markers to detect them, the different methods used, and the utility of their detection in identifying men with prostate cancer and as a prognostic factor.

The discovery of Toll-like receptors (TLRs) about 20 years ago was a remarkable achievement not only in the field of immunology but also in the field of medicine. The TLRs are a family of pattern recognition receptors which play an important role in immune responses by recognizing pathogen-associated molecular patterns. The TLRs also recognize danger-associated molecular patterns, which are associated with some diseases such as cancer. Recent evidence shows that TLRs are expressed not only in immune cells but also in tumor cells. The TLRs appear to play a role in tumor progression and treatment. Most likely, TLR activation has an impact on the initiation, development and treatment of tumors by modulating the inflammatory microenvironment. However, the activation of TLRs contributes to both inhibition and promotion of various tumors, with unclear underlying mechanisms. In this review article, the authors elucidate their current understanding about the role of TLRs in tumor progression, as well as the recent progress in utilizing TLR agonists as potential therapeutic agents in cancer treatment.

Aim: Excision repair cross complementation group 1 (ERCC1) has a key role in enhanced DNA damage repair caused by oxaliplatin-based therapy and may lead to resistance of these platinum drugs in colorectal cancer (CRC) patients. Hence, the present preliminary study aimed to explore the role of ERCC1 C/T polymorphism at codon 118 as well as its immunoreactivity in patients with primary CRC. Methods: ERCC1 polymorphism was studied using PCR-RFLP and ERCC1 protein expression was examined by immunohistochemistry in 50 CRC patients. Results: ERCC1 codon 118 C/T polymorphism analysis reported the predominance of C/T (52%) genotype as compared to C/C (38%) and T/T (10%) genotypes. Furthermore, 72% of patients showed positive ERCC1 protein expression. Significant correlation was not observed between clinicopathological parameters and ERCC1 polymorphism, while ERCC1 protein expression significantly correlated only with tumor site (colon vs. rectum) (P = 0.046). Further, the present study failed to demonstrate the role of ERCC1 C118T polymorphism or protein expression as useful prognostic markers in CRC patients. Conclusion: ERCC1-positive protein expression may be a useful marker for rectal cancer patients. However, further evaluation in a larger set of CRC patients is required to better understand the role of ERCC1.