The two major histologic subtypes of esophageal cancer have different risk factors as well as different molecular mechanisms. In this review, the differences in risk factors and genetic/epigenetic alterations between esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) will be discussed. Cigarette smoking and alcohol consumption are risk factors for ESCC, while gastroesophageal reflux, cigarette smoking, and obesity are the main EAC risk factors. Commonly mutated genes of both subtypes are TP53 and PIK3CA. Recent genome-wide analysis revealed that the activation of the RAC1 pathway may contribute to EAC tumorigenesis. Clustered abnormality in copy number was observed in several genes in ESCC, whereas a few genes were specifically altered at high frequency in EAC. Epigenetic changes, such as DNA methylation, histone modifications, and altered expression of microRNAs, have been revealed to influence carcinogenesis and progression of both ESCC and EAC.

The success of targeted therapies for cancer patients rests on three major components: the right target(s), the right drug and drug combination, and the right patient population. Although much progress has been made in understanding the mechanism of disease and in refi ning pharmaceutical properties of therapeutic agents, the attrition rates between target discovery and drug marketing approval have been high, especially in oncology. One of the main reasons underlying this undesirable statistics is believed to be the lack of predictive power of the model systems used in the preclinical setting. Several strategies have been employed with the aim of improving the predictive value of the preclinical studies, such as incorporating genomic profi ling and molecular segmentation into model selection, and enhancing the development and application of patient-derived xenograft models even during early stage of drug discovery. This brief review will summarize some of the recent concept and practice in incorporating patient-derived models into all stages of drug discovery process, from target to clinical development.

Aim: The aim was to evaluate the potential influences of cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphisms on breast cancer risk, the distribution of CTLA-4 single nucleotide polymorphisms (1661AG) in breast cancer patients and control subjects was investigated.

Methods: In this case-control study, 100 patients with breast cancer as case group and 100 healthy participants as a control group were compared. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Demographic characteristics of the study population, as well as tumor size, tumor grade and stage were collected in a questionnaire designed for this study. The collected data were statistically analyzed by SPSS-16.0 (SPSS Inc., Chicago, USA) predictive analytic software using the Chi-square test.

Results: The mean age of women was 43.42 ± 13.1 years. The AA genotype was frequent in case group (43%) whereas the AG genotype was found more in the control group (69%). There was no significant relationship between the studied polymorphisms and the grade, stage and size of the tumor, nor between the studied polymorphisms and estrogen receptor, progesterone receptor and lymph node involvement (P > 0.05). Significant association between the studied polymorphisms and breast cancer metastases was found (P = 0.02).

Conclusion: According to the results of the study, the AA genotype is associated with breast cancer, but none of the studied gene polymorphisms is associated with prognostic factors such as tumor stage, grade or size.

Aim: Previous studies demonstrated discordant expression of human epidermal growth-factor receptor 2 (HER2) between primary cancer and their recurrence/metastasis. This study further evaluated HER2 status between primary gastric and breast invasive carcinomas and paired metastatic disease to lymph nodes.

Methods: This study collected formalin-fixed paraffin-embedded representative tissue blocks from 62 gastric and 65 breast primary carcinomas as well as synchronous metastatic lymph nodes (male:female = 39:88; age ranged between 44 and 95 years with mean age of 69.32 years) for immunohistochemical staining of HER2 expression (DAKO HercepTest™ kit). If immunohistochemical HER2 score reached to 2+, HER2 amplification was then assessed using fluorescence in situ hybridization (PharmDx™ kit DAKO).

Results: The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.67% in primary gastric carcinoma and corresponding nodal metastasis, while the changes in HER2 expression were revealed in 4.61% of mammary and lymph node neoplastic samples. A high-level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was confirmed in both types of cancer; the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity, mostly appreciable in gastric cancer.

Conclusion: In any case, the shift from positive to negative HER2 expression suggests that trastuzumab could be the targeted treatment choice whereas the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes.

Aim: This retrospective study was performed to show the incidence of bone metastasis from carcinoma of the buccal mucosa. Head and neck cancer is a leading health problem in India due to an increased incidence of tobacco use and poor oral hygiene. Squamous cell carcinoma of the buccal mucosa is common and roughly 2.5% of all malignancies that present to our center. Moreover, most patients present at late stages (III/IV) and consequently, survival rates are low. Bone metastasis in advanced cases of such carcinomas is rarely reported worldwide but is more prominent in parts of India.

Methods: Here, we present a series of patients diagnosed with buccal mucosa carcinomas within the past 5 years that also demonstrated bone metastases.

Results: These patients were young, with a history of tobacco chewing with locally advanced disease and bone metastases that developed within one year of diagnosis. Flat bones and vertebrae were mainly involved and the survival was short after diagnosis of metastasis despite treatment with local radiotherapy and chemotherapy. The cause of such frequent metastases cannot be proved but subclinical seeding of malignant cells before the eradication of the primary tumor is probable contributory with advanced local and nodal disease with high grade tumor.

Conclusion: A pretreatment bone scan should be performed in locoregionally advanced buccal mucosa carcinomas at the time of diagnosis to define the treatment plan.

Early stage carcinoma of the tonsil is curable, and the incidence of systemic metastasis is very low and central nervous system involvement is very rare. A patient diagnosed with early stage tonsillar carcinoma treated with chemoradiation was followed by brachytherapy boost. One and half years after completion of treatment, the patient presented with disseminated metastasis to the skin, lung, liver, bone, and brain. He had all favorable prognostic parameters except being a young adult.

Prostate cancer is the most common type of male malignancy in the world and approximately 10-20% of prostate cancer shows a metastatic disease at initial diagnosis commonly to the bones, vertebrae, ribs, long bones, and skull. However, prostate cancer metastasis to the omentum with malignant ascites is extremely uncommon. In this study, we report such a case, which also highlights a repeatedly negative ascetic fluid cytology even with multiple omental metastatic nodules. The purpose of this case report is to provide awareness to physicians for this rare occurrence.

Glioblastoma multiforme is the most common type of primary central nervous system tumor and is noted for its short survival and poor response to chemotherapeutic agents. Unfortunately, the relapse rate is very high, and there is no reference drug for second-line treatment. In this study, a patient was treated with the Soffietti regimen. The induction phase was fotemustine 75 mg/m² at day 1 and day 8 and bevacizumab 10 mg/kg at day 1 and day 15. The maintenance phase was fotemustine 75 mg/m² and bevacizumab 10 mg/kg every 3 weeks for two cycles. Follow-up magnetic resonance imaging showed post-surgical changes at the left occipital level, without contrast enhancement, and toxic left leuko-encephalopathy post-treatment without mass effect and with no evidence of tumor residue. The patient then was maintained with bevacizumab monotherapy until it was withdrawn when pulmonary thromboembolism occurred. Following tumor regrowth, fotemustine was started again as maintenance therapy. The patient achieved stabilization of his disease until his death due to thromboembolic and infectious complications.

Unusual site metastasis as a presenting complaint of renal cell carcinoma (RCC) has been reported previously in the literature. RCC is a tumor with notoriously unpredictable behavior. The authors report an unusual case of metachronous bilateral testicular metastasis in a patient who operated for RCC. The case highlights the unique behavior of RCC with an unusual site of metastasis. A 72-year-old patient presented with bilateral scrotal swelling of 1-month duration. There was a history of left radical nephrectomy for RCC 4 years prior. He underwent a bilateral high inguinal orchidectomy and diagnosis of chromophobe RCC was made on histopathological examination.

Circulating tumor cells (CTCs) have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer. Over the past few years, they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream. This process can also occur at an early stage of cancer. The major limitation in isolation of CTCs is their availability in limited numbers. Hence, many techniques have been developed and are under continuous improvement to enhance their efficacy of CTC isolation and enumeration. They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information. They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease. Hence, detecting and characterizing CTCs can definitely become an inevitable step in treating solid tumor malignancies. In this review, we have tried to comprehend the basics of CTCs including isolation, detection, characterization, and molecular mechanism of their circulation in the blood stream. We have mostly focused on the significance of CTCs in diagnosis and therapies of four most common types of cancers, namely, breast, prostate, lung, and colorectal. This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

Urothelial bladder carcinoma (UBC) is an intricate malignancy with a variable natural history and clinical behavior. Despite developments in diagnosis/prognosis refinement and treatment modalities, the recurrence rate is high, and progression from non-muscle to muscle invasive UBC commonly leads to metastasis. Moreover, patients with muscle-invasive or extra-vesical disease often fail the standard chemotherapy treatment, and overall survival rates are poor. Thus, UBC remains a challenge in the oncology field, representing an ideal candidate for research on biomarkers that could identify patients at increased risk of recurrence, progression, and chemo-refractoriness. However, progress toward personalized medicine has been hampered by the unique genetic complexity of UBC. Recent genome-wide expression and sequencing studies have brought new insights into its molecular features, pathogenesis and clinical diversity, revealing a landscape where classical pathology is intersected by the novel and heterogeneous molecular groups. Hence, it seems plausible to postulate that only an integrated signature of prognostic/predictive biomarkers inherent in different cancer hallmarks will reach clinical validation. In this review, we have summarized ours and others’ research into novel putative biomarkers of progression and chemoresistance that encompass several hallmarks of cancer: tumor neovascularization, invasion and metastasis, and energy metabolism reprogramming of the tumor microenvironment.

Aim: Medulloblastoma (MB) is the most common malignant brain tumor in children. The crucial role of extracellular-microRNAs (ex-miRNAs) in cancer has been widely recognized; however, their role in MB remains unknown. This study aimed to investigate MB-driven ex-miRNAs.

Methods: Microarray analysis was used to disclose the identity and quantity of key miRNAs excreted in culture-medium (CM) of 3 human MB cell lines and cerebrospinal fluid (CSF) of brain tumors (including MB) and leukemia patients. MiRNA expression was validated by quantitative reverse transcription polymerase chain reaction.

Results: We have demonstrated that the 3 MB cell lines tested commonly expressed 1,083 miRNAs in their spent CM. Among them, 57 miRNAs were specific to the CM of metastasis-related cell lines which represents the aggressive group 3 and group 4 MB subtypes. A significant number (1,254) of ex-miRNAs were identified in the CSF of a MB patient. Eighty-six of these miRNAs were found to be differentially expressed in this patient’s CSF compared with controls. Interestingly, 3 metastasis-associated miRNAs over-represented in CM of metastasis-related MB cell lines were found to be significantly enriched in the CSF of the MB patient.

Conclusion: Although more samples are required to fully verify these results, our work provides the first evidence for the presence of a significant amount of miRNAs excreted extracellularly by MB cells and raises the possibility that, in the near future, miRNAs could be probed in CSF of MB patients and serve as novel biological markers.

Aim: Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the standard treatment for patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCNHL). Nevertheless, anthracyclines are contraindicated for some patients, e.g. cardiac dysfunction, severe hepatic dysfunction, jaundice. Thus, this study assessed the effectiveness of non-anthracycline chemotherapy regimen cyclophosphamide, vincristine, and prednisone (CVP) in elderly DLBCNHL patients vs. the standard CHOP.

Methods: This retrospective study included 418 DLBCNHL patients diagnosed between 2003 and 2006 and followed until March 2014. During this period of time, rituximab was not available for all patients, particularly for patients older than 60 years.

Results: CHOP and CVP were administered to 351 (84%) and 67 (16%) patients, respectively. Older age and comorbidities, particularly cardiovascular and diabetes mellitus, were independent determinants for not receiving CHOP. Patients received more courses of CHOP treatment than that of CVP (6 vs. 3 courses; P < 0.001) and developed more toxicities (48.4% vs. 23.9%; P < 0.001), particularly fatigue, alopecia, and gastrointestinal tract toxicities. Complete response rate was higher in CHOP than in CVP (69.9% vs. 29.9%; P < 0.001). Moreover, early death was significantly higher in CVP group of patients than in CHOP (43.3% vs. 8.6%; P < 0.001). After a median follow-up of 71 months, the median overall survival (OS) and event-free survival (EFS) were significantly better in CHOP than in CVP (49.5 vs. 3.7 months and 32.2 vs. 3.5 months; P < 0.001 for both, respectively). Older age, poor age-adjusted International Prognostic Index scores, not receiving CHOP or consolidative radiotherapy were independent predictors of poor OS and EFS.

Conclusion: Use of the CVP regime to treat DLBCNHL patients who were unfit to the standard CHOP treatment was associated with lower remission rates and poorer EFS and OS in this group of patients.

Aim: The aim was to analyze the expression of novel biological transcription markers, forkhead-box A1 (FOXA1), GATA binding protein 3 (GATA-3), and established markers such as Ki-67 (MIB-1) and human epidermal growth factor receptor 2 (HER2) in estrogen receptor (ER(+)) and ER(-) ductal carcinoma in situ (DCIS) patients with/without recurrence.

Methods: Two hundred and ninety-one cases of DCIS were retrieved from our pathology database, with complete data available for 219 cases. The follow-up period is from 1988 to 2009. Recurrence is defined in terms of DCIS or invasive carcinoma (IC). No recurrence was seen in 88% (196/219) of cases; 12% (26/219) had a recurrence (IC: 13, DCIS: 13). We are reporting the results of biological marker expression in terms of recurrence and ER status.

Results: Our study demonstrates strong expression of GATA-3 in the ER(+) DCIS in recurrence and nonrecurrence groups similar to previously described in IC. A reduced expression of GATA-3 was observed in ER(-) recurrence and nonrecurrence groups. A strong HER2 protein expression, as well as high proliferation index, was seen in recurrence group (DCIS and IC). FOXA1 expression is reduced across the groups though not statistically significant.

Conclusion: This is the first study to analyze novel transcription markers FOXA1 and GATA-3 in DCIS. Further work needs to be done on a larger cohort of DCIS cases with recurrence to better understand, which variables are best able to predict recurrence and guide therapy decision strategies. Maintenance of FOXA1 and GATA-3 expression in ER(-) DCIS may offer new promising targets for therapy in future.

Aim: Primary lung cancer is the leading cause of human cancer deaths worldwide, and squamous cell carcinoma (SCC) is one of the most frequent histologic subtypes. The aim of our study was to analyze clinical factors potentially affecting the overall outcome of advanced lung SCC patients.

Methods: A series of 72 consecutive patients with advanced SCC undergoing chemotherapy at our institution between January 2007 and July 2013 were eligible for our analysis.

Results: By univariate analysis, a better overall survival (OS) was related to response to first-line chemotherapy: median OS were 19.7 vs. 7.17 months, respectively, for responders and nonresponders patients (P < 0.0001). Eastern Cooperative Oncology Group performance status, gender, and surgery were other prognostic factors. No significant relationship between OS and smoking status, age, body mass index, or type of treatment was found. In the third-line setting, a better OS was associated with objective response to second-line treatment (P = 0.015).

Conclusion: Our results suggest that differences in OS seem strictly associated with clinical response to previous treatments. These data should be considered in the therapeutic strategy and management of patients with SCC of the lung.

Aim: The aim was to examine the anti-proliferative effect of a Withania somnifera (WS) root extract in cell cultures and nude mouse xenografts of breast cancer cell line MDA-MB-231.

Methods: WS root extract was used to treat tumor cells at concentrations up to 100 ug and for nude mouse experiments, the mice received daily WS at 300 mg/kg by oral gavage for 8 weeks.

Results: The WS extract reduced viability of MDA-MB-231 cells by 75% and 88% after exposure of the cells to 50 and 100 ug/mL, respectively, compared to vehicle-treated controls. WS extract caused a dose-dependent increase in the percentage of cells in the sub-G1 phase compared to untreated controls by 6% and 10% after exposure to 25 and 50 ug/mL WS extract, respectively. WS extract also inhibited proliferation of xenografted MDA-MB-231 cells. The WS extract caused reductions in xenograft size by 60% compared to the untreated control after 8 weeks of treatment. Six of ten mice in the control group showed tumor metastasis to the lung, whereas there was none in the mice treated with the WS extract. At the gene level, WS caused a 75% reduction in chemokine CCL2 expression (P < 0.05) in the xenografted tumors of the treated mice.

Conclusion: WS root extract inhibited proliferation of breast cancer cells in vitro and in vivo and significantly reduced expression of the cytokine, CCL2. These results warrant further studies to assess the underlying molecular mechanism of the anti-tumor activity of the WS extract in breast cancer.

Cancer of unknown primary site is a group of uncommon cancers where patients present with metastatic disease and the primary site is not identified, even after a complete workup to establish the diagnosis. Inguinal metastasis with unknown primary is even more uncommon, and histological type is the most important guiding factor to look for the primary. This report describes the rare situation of inguinal metastasis with an unknown primary site where a combination of squamous and transitional cell carcinoma was found on final histopathology. It highlights the importance of multimodality approach including an aggressive surgical resection combined with adjuvant radiation therapy to achieve an optimal outcome.

Pulmonary and liver metastases are common sites of distant metastasis from the rectal carcinoma. Metastases to the head and neck region are uncommon from carcinoma of the rectum, and orbital metastases are extremely rare. Here, we describe a 27-year-old female, who was diagnosed as a case of anorectal carcinoma in April 2010. She underwent abdominoperineal resection followed by concurrent chemoradiotherapy and adjuvant chemotherapy with 5 fluorouracil and leucovorin on follow-up. In January 2012, she presented with gradually increasing swelling over the left temporal region and left sided proptosis. Fine-needle aspiration and a cell block were performed. Metastasis was confirmed histologically. Palliative radiotherapy to the left orbit at the dose of 3 Gy per fraction 10 fractions to a total dose of 30 Gy was given by cobalt-60. In patients with a history of rectal carcinoma, recent onset proptosis with temporal swelling, although rare, should raise suspicion of metastatic deposit.

Spinal intradural mature teratomas are rarely encountered in adults. In this report, one of the oldest patients ever reported to harbor an intradural mature teratoma of the conus medullaris is presented, and the relevant literature concerning the teratoma’s origin, clinical presentation, radiological features, and treatment modalities is reviewed. A previously healthy 70-year-old woman presented with a 2-month history of left sciatica. Her neurological examination was normal and the magnetic resonance imaging of the thoracolumbar spine showed an intradural, partially cystic mass extending from T12 to L3 level. The patient underwent a T11-L4 laminectomy. After opening the dura, a yellowish vascular tumor attached to the conus medullaris came into view. Meticulous dissection allowed for subtotal tumor removal. Only a thin part of the tumor wall, tightly attached to the conus medullaris, was left. The tumor was diagnosed as mature teratoma by histological study, and no adjunctive therapy was administered. The pain experienced by the patient disappeared postoperatively. Her condition remained unchanged with no radiological recurrence through the most recent follow-up examination, 3 years after surgery. The present study outlines that mature teratoma can arise from the conus medullaris, even in older adult patients. Functional preservation is of utmost importance, and long-term follow-up is mandatory to spot recurrences early.

Epigenetic alterations, including DNA methylation, histone modification, loss of genome imprinting, chromatin remodeling and noncoding RNAs, are associated with human carcinogenesis. Among them, DNA methylation is a fundamental epigenetic process to modulate gene expression. In cancer cells, altered DNA methylation includes hypermethylation of site-specific CpG island promoter and global DNA hypomethylation. Detection of aberrant gene promoter methylation has been applied to clinic to stratify risk in cancer development, detect early cancer and predict clinical outcomes. Environmental factors associated with carcinogenesis are also significantly related to aberrant DNA methylation. Importantly, epigenetic changes, including altered DNA methylation, are reversible and thus, used as targets for cancer therapy or chemoprevention. An increasing number of recent studies reported DNA methylation level to be a useful biomarker for diagnosis, risk assessment and prognosis prediction for gastrointestinal cancers. This review summarized the accumulated evidence for clinical application to use aberrant DNA methylation levels in gastrointestinal cancers, including colorectal, gastric and esophageal cancer.

Esophagogastric junctional adenocarcinoma is commonly treated as esophageal adenocarcinoma (EAC), and has dramatically increased in Western countries for several decades. The similar trend has been observed in Asian countries (not in China). Barrett's esophagus (BE) is a widely accepted precursor of EAC. Recent advances of next-generation sequencing could provide researchers with a better understanding of genetic and epigenetic alterations in the carcinogenesis of EAC. In this review, we have summarized the recently reported major genetic and epigenetic alterations in both BE and EAC. Sonic hedgehog/bone morphogenetic protein axis, which is a key signaling for esophageal development, plays an important role in BE intestinal metaplasia. Single nucleotide polymorphisms related to esophageal organogenesis, such as FOXF1 and FOXP3, are frequently detected in BE patients. During progression of BE to adenocarcinoma, lacking of normal function of TP53 and CDKN2A by loss of heterozygosity (LOH), mutation, or promoter methylation has been frequently observed. LOH at 9p (coding CDKN2A) is an earlier event to EAC carcinogenesis compared to that at 17q (coding TP53) LOH. In order to further elucidate the pathogenesis of BE and EAC, it will be necessary to analyze these genetic/epigenetic alterations in combination with clinical data in a large-scale cohort.

Circulating tumor cells (CTCs) are originated from the primary tumor lesion into the blood stream. CTCs could lead to recurrence of gastrointestinal (GI) cancers, even after a curative resection and colonizing in the distant organs to facilitate tumor distant metastasis; however, it has been challenging in clinic to detect CTCs for a long time, such as detection methodology or molecular markers for identification of CTCs. This review discussed the recent technical advances and biomarkers in the detection of CTCs and the molecular mechanism of CTC in cancer progression and metastasis. Moreover, novel concepts, such as cancer stem cells and epithelial-mesenchymal transition, could lead to CTCs and tumor progression and metastasis. Nevertheless, the involvement of CTCs varies greatly among cancer types in the GI and much remains to be learned. Thus, further study will provide more insightful information from a clinical and translational viewpoint to use CTCs for cancer early diagnosis or prediction of tumor recurrence and investigation of tumor progression and metastasis as well.

Chronic inflammation has been identified as an important risk factor in development of the gastrointestinal (GI) tract cancers and the underlying molecular mechanisms have been studied extensively. Chronic inflammation is able to trigger cellular events to promote malignant transformation of normal epithelial cells in the gastrointestinal tract to cancer. Host inflammation responses in carcinogenesis are through multiple mechanisms, such as reactive oxygen and nitration species from mononuclear phagocytes and leukocytes, immune response, and pro-inflammatory cytokines. Nuclear factor κB(NF-κB) has been considered as the central mediator of the immune response. Activation of NF-κB by phosphorylation leads to translocation of NF-κB protein to the nucleus and in turn regulates transcription of several pro-inflammatory cytokines and chemokines. Furthermore, chronic inflammation creates an environment forgenomic and epigenetic changes. In this review, we summarize important molecular mechanisms that link chronic inflammation and GI tract cancer, including esophageal, gastric and colonic cancers, focusing on infective and noninfective agents such as gastroesophageal reflux disease, Helicobacter pylori gastritis and inflammatory bowel disease.

Gastrointestinal (GI) cancers remain one of the most common malignancies and are the major cause of cancer deaths worldwide. Significant advancements have improved our understanding of the pathogenesis and pathology of GI cancers, but high mortality rates, an unfavorable prognosis, and lack of clinical predictive biomarkers provide an impetus to investigate novel diagnostic/prognostic markers and therapeutic targets for GI cancers. MicroRNAs (miRNAs) are short (19-24 nucleotides), non-coding RNA molecules that regulate gene expression at the post-transcriptional level, thus playing an important role in modulating various biological processes. This includes developmental processes, proliferation, apoptosis, metabolism and differentiation, all involved in initiation and progression of various human cancers. Aberrant miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor- and tissue-specific expression profiles, stability, and the availability of robust clinical assays for their detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic/prognostic tools and therapeutic targets, thus potentially illuminating future treatment strategies for GI cancers.

Colorectal cancer remains a significant cause of cancer-related mortality worldwide, mainly because of tumor relapse and metastases. Cancer stem cells (CSCs) are considered to be the main cause of resistance to chemotherapeutic agents, as well as being responsible for distant metastases. Although CSCs themselves possess innate abilities for self-renewal and differentiation, the environment surrounding CSCs provides oxygen, nutrients and secreted factors, and also supports angiogenesis, thus it's responsible for maintaining their CSC properties. Furthermore, extensive investigations have revealed that obesity, accompanied by excess visceral adipose tissue, induces chronic inflammation, and is linked to the risk and progression of several gastrointestinal cancers, through modulating the capacities of the CSCs. This review presents the evidence linking colorectal CSCs and their environment and summarizes our current understanding of the molecular mechanisms underlying this relationship.

Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal (GI) cancers have recently gained considerable attention. In addition to agents targeting vascular endothelial growth factor (VEGF), epidermal growth factor receptor, the multi-kinase inhibitor, and regorafenib have also become available for the treatment of metastatic colorectal cancer patients. Currently, trastuzumab, an antibody targeting human epidermal growth factor receptor-2 (HER-2), in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive gastric cancer (GC). The efficacy of ramucirumab, a human monoclonal antibody that inhibits VEGF from binding to its receptor in GC, has also been recently demonstrated. At present, a great number of novel targeted drugs are in pre-clinical or clinical studies. In this review, we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating GI cancers, with a focus on emerging strategies for personalized treatment.

Cancer cells exhibit altered glucose metabolism, mitochondrial dysfunction, anaerobic glycolysis, and upregulation of the pentose phosphate pathway (PPP). Recent genetic and metabolic analyses have provided insights into the molecular mechanisms of genes that are involved in alteration of cancer metabolism and tumorigenesis. Hypoxic induced factor 1 regulates the reciprocal relationship between glycolysis and oxidative phosphorylation, and p53 also modulates the balance between the glycolytic pathway and oxidative phosphorylation. Mitochondria function in cancer differs from that in normal cells owing to mutations of mitochondrial DNA and alterations of metabolism. Overexpression of transcription factors, metabolite transporters, and glycolytic enzymes is observed and associated with poor prognosis, and it may be associated with chemoradiotherapy resistance in multiple cancer cell types. The PPP plays a critical role in regulating cancer cell growth by supplying cells with ribose-5-phosphate and nicotinamide adenine dinucleotide phosphate for detoxification of intracellular reactive oxygen species (ROS), reductive biosynthesis, and ribose biogenesis. ROS levels increase during carcinogenesis owing to metabolic aberrations. This review discusses alterations of mitochondrial metabolism, anaerobic glycolysis, the PPP, and control of ROS levels by the endogenous antioxidant system in cancer, as well as the novel small molecules targeting these enzymes or transporters that exert antiproliferative effects.

Epithelial-mesenchymal transition (EMT) was first reported as an essential process in embryonic cells and later showed that cancer cells, regardless of the context, exhibit a similar phenomenonthat is crucial for tumor progression. Epithelial cells lose their adhesive characteristic capacity which is necessary for their functions but gain a mesenchymal phenotype. This change from epithelial to mesenchymal phenotype of cancer cells makes it difficult tounderstand the mechanism underlying cancer biology and tumor progression. A number of transcription factors involved in tumor cell EMT and miRNA-regulated EMT have been reported. This review discussed recent findings and new players in EMT in gastrointestinal cancers. Since the molecular mechanisms of tumor progression are sometimes context dependent, the recent findings of EMT have been reviewed in the context-dependent manner.

Genetic, epigenetic and somatic changes deregulate the expression of growth factor receptors (GFRs), leading to cancer initiation and progression. Tumor cell growth and survival are orchestrated by clonal expansion and evasion of apoptotic signals in cancer cells. The growth of cells is further supported by angiogenesis and metastasis to distant organs. High expression of GFRs also contributes to the development of resistance. Therefore, therapeutics to target GFRs is a potentially attractive molecular approach to treat cancer more effectively. In this review, we have discussed the contribution of GFRs to cancer development and addressed molecular approaches undertaken to inhibit GFR-mediated pathways. A wide number of monoclonal antibodies (mAbs) and protein kinase inhibitors targeting these GFR-mediated functions are in clinical trials to treat human malignancies. However, most drugs that target GFRs lead to the development of drug resistance and generate adverse effects. Nucleic acid-based therapeutics, e.g. short interfering RNA (siRNA) could be harnessed to selectively silence GFR genes in cancer cells. Different polymer, liposome-based nanocarriers, and the most recently developed pH-sensitive inorganic carbonate apatite nanoparticles have been used in cell culture and preclinical trials for cytoplasmic delivery of the siRNAs targeting different GFR genes. siRNA-based therapeutics have been shown to have significant potential to suppress GFR expression and functions and thus could be developed as molecular therapeutics. Multi-targeting of tumors at different levels by combining various approaches along with chemotherapy would be a promising therapeutic approach to fight the disease. Suitable nanocarriers capable of entrapping siRNA, mAb, GFR inhibitors and classical drugs targeting GFR have potential therapeutic applications.

Aim: The aim was to describe, in a prospective manner, the clinical, histopathological and epidemiological characteristics of lung cancer patients who attended as outpatients at the Lluís Alcanyís, Xàtiva Medical Oncology Hospital, València, Spain from January 2004 to July 2014. We also analyzed survival and compared our data with that reported in the literature.

Methods: Clinical and demographic characteristics were analyzed for the entire series and trends were compared by year of diagnosis. Changes in epidemiology were examined and compared.

Results: There were 701 patients (91.4% were men, mean age 67.6). Main histology was squamous cell carcinoma (41.5%). Squamous cell carcinoma prevailed in men (45.5%) and adenocarcinoma (ADC) in women (60.3%). The percentage of men with lung cancer and of patients with squamous cell carcinoma was higher than in the reported worldwide data and remained throughout the 10 years period. Mean survival was low, with < 10% survivors at 5 years. Stage of disease remained the main prognostic factor for survival.

Conclusion: Squamous cell carcinoma continues to be the most frequent histological type in our area. Male and smoking is associated with lung carcinoma while ADC more often occurs in females. Over the time, our epidemiological and histological patterns have not changed, possibly in relation to maintenance of smoking habits.

Diagnosis of leukemia during pregnancy is a dramatic event that poses challenges to the pregnant woman, the family, and physicians. Chronic myeloid leukemia (CML) comprises up to 10% of pregnancy-associated leukemia. There is no specific guideline for CML management in pregnant women. This study reported a case of successful pregnancy after 12 years of chemotherapy including tyrosine kinase inhibitor for CML. Pregnancy after 12 years of continuous chemotherapy is rare, which also led a challenge for medical oncologists and patient as well. This study described the assessment of the risk balance and benefit and management of such a patient.