Extended dosing (12 cycles) vs conventional dosing (6 cycles) of adjuvant temozolomide in adults with newly diagnosed high-grade gliomas: a randomized, single-blind, two-arm, parallel-group controlled trial.

Purpose: Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas. Methods: Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months. Results: A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months. Conclusion: Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles. Trial registration: Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal-based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosome-- mediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

Evaluation of the effects of simulated hypoxia by CoCl2 on radioresistance and change of hypoxia-inducible factors in human glioblastoma U87 tumor cell line.

PURPOSE: Glioblastoma (GBM) is considered the most common and lethal type of brain tumor with a poor prognosis. GBM treatment has challenges due to its aggressive nature, which often causes treatment failure and recurrence. Hypoxia is one of the characteristics of glioblastoma tumors that contribute to radioresistance and malignant phenotypes of GBM. In this study, we aimed to determine the effects of hypoxia on the radiosensitivity of U87 GBM cells by the hypoxia-mimicking model. METHODS: Following the treatment of cells with different concentrations of CoCl2, an MTT assay was used to evaluate the cytotoxicity of CoCl2. To understand the effects of Ionizing radiation on CoCl2-treated groups, cells were exposed to irradiation after pretreating with 100 µM CoCl2, and a clonogenic survival assay was performed to determine the radiosensitivity of U87 cells. Also, the intracellular Reactive oxygen level was measured by 2',7'-dichlorofluorescein diacetate (DCFDA) probe staining. Additionally, the expression of hypoxia-associated genes, including HIF-1α, HIF-2α, and their target genes (GLUT-1), was monitored by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Our study revealed that the cell viability of CoCl2-treated cells was decreased in a concentration-dependent manner. Also, CoCl2 did not cause any cytotoxicity on U87 cells at a concentration of 100 µM after treatment for 24 h. Colony formation assay showed that CoCl2 pretreatment induced radioresistance of tumor cells compared to non-treated cells. Also, CoCl2 can protect cells against irradiation by the clearance of ROS. Moreover, Real-time results showed that the mRNA expression of HIF-1α and GLUT-1 were significantly upregulated following hypoxia induction and/or irradiation condition. However, the level of HIF-2α mRNA did not change significantly in hypoxia or irradiation alone conditions, but it increased significantly only in hypoxia + irradiation conditions. CONCLUSION: Taken together, our results indicated that simulating hypoxia by CoCl2 can effectively increase hypoxia-associated genes, specially HIF-1α and GLUT-1, but did not affect HIF-2α gene expression. Also, it can increase the clearance of ROS, respectively, and it leads to inducing radioresistance of U87 cells.

Insight into RNA-based Therapies for Ovarian Cancer.

Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.

Current use of Molecular Mechanisms and Signaling Pathways in Targeted Therapy of Prostate Cancer.

Prostate cancer (PC) is identified as a heterogeneous disease. About 20 to 30% of PC patients experience cancer recurrence, characterized by an increase in the antigen termed serum prostate-specific antigen (PSA). Clinical recurrence of PC commonly occurs after five years. Metastatic castration-resistant prostate cancer (mCRPC) has an intricate genomic background. Therapies that target genomic changes in DNA repair signaling pathways have been progressively approved in the clinic. Innovative therapies like targeting signaling pathways, bone niche, immune checkpoint, and epigenetic marks have been gaining promising results for better management of PC cases with bone metastasis. This review article summarizes the recent consideration of the molecular mechanisms and signaling pathways involved in local and metastatic prostate cancer, highlighting the clinical insinuations of the novel understanding.

Dual targeting of TGF-ß and PD-L1 inhibits tumor growth in TGF-ß/PD-L1-driven colorectal carcinoma.

Immunosuppressive factors within the tumor microenvironment (TME), such as Transforming growth factor beta (TGF-ß), constitute a crucial hindrance to immunotherapeutic approaches in colorectal cancer (CRC). Furthermore, immune checkpoint factors (e.g., programmed death-ligand 1 [PD-L1]) inhibit T-cell proliferation and activation. To cope with the inhibitory effect of immune checkpoints, the therapeutic value of dual targeting PD-L1 and TGF-ß pathways via M7824 plus 5-FU in CRC has been evaluated. Integrative-systems biology approaches and RNAseq were used to assess the differential level of genes associated with 88 metastatic-CRC patients. The level of PD-L1 and TGF-ß was evaluated in a validation cohort. The anti-proliferative, migratory, and apoptotic effects of PD-L1/TGF-ß inhibitor, M7824, were assessed by MTT, wound-healing assay, and flow cytometry. Anti-tumor activity was assessed in a xenograft model, followed by biochemical studies and histological staining, and gene/protein expression analyses by RT-PCR and ELISA/IHC. The result of differentially expressed genes (DEGs) analysis showed 1268 upregulated and 1074 downregulated genes in CRC patients. Among the highest scoring genes and dysregulated pathways associated with CRC, PD-L1, and TGF-ß were identified and further validated in 92 CRC patients. Targeting of PD-L1-TGF-ß inhibited cell growth and migration, associated with modulation of CyclinD1 and MMP9. Furthermore, M7824 inhibited tumor growth via targeting TGF-ß and PD-L1 pathways, resulting in modulation of inflammatory response and fibrosis via TNF-α/IL6/CD4-8 and COL1A1/1A2, respectively. In conclusion, our data illustrated that co-targeting PD-L1 and TGF-ß pathways increased the effect of Fluorouracil (5-FU) and reduced the tumor growth in PD-L1/TGF-ß expressing tumors, providing a new therapeutic option in the treatment of CRC.

[68Ga] Ga-Pentixafor diffuse bilateral Adrenal & Breast uptake in a patient with High-grade Glioma: A note of caution on normal variants.

[68Ga] Ga-labeled C-X-C motif receptor4 as a novel radio-ligand using PET/CT has been investigated for tracing various kinds of solid and hematopoietic malignancies in recent years. High-grade Glioma (WHO classification 2016 grade III and IV) shows elevated levels of CXCR4 ligand expression in the affected tumoral cells. Healthy and non-affected organ cells express low-level CXCR4 ligands density. We performed [68Ga] Ga-Pentixafor (Pars-Cixafor™) PET/CT in a patient with high-grade Glioma (anaplastic oligodendroglioma WHO grade III) with no other documented medical condition and history. In addition to the Pentixafor-avid tumor remnant in the PET/CT images, we observed mild symmetrical bilateral uptake in the fibro glandular tissue of the breasts and moderate CXCR4(Pentixafor) avidity in both adrenal glands without any discernable pathology and abnormal density changes in the CT component of the study. Attention should be paid to the interpreting [68Ga] Ga-Pentixafor PET/CT examination and its normal uptakes and variants.

Outcome of Second Line Treatment of Recurrent High- Grade Glioma by re-Irradiation or Bevacizumab-based Chemotherapy: A Cross Sectional Study.

INTRODUCTION: Currently, there is no standard of treatment for the management of the recurrent high-grade glioma. Re-resection, re-irradiation, and chemotherapy are among main treatment options without any proven efficacy. AIM: To compare the outcome of second line treatment of recurrent high-grade glioma by re-irradiation or bevacizumab-based chemotherapy. METHODS: Retrospectively, patients with the recurrent high-grade glioma treated by re-irradiation (ReRT group) (34 patients) or bevacizumab-based chemotherapy (Bev group) (40 patients) as the first-file after the first recurrence were compared in term of first-line progression free survival (PFS), second-line PFS, and overall survival (OS). RESULTS: Both groups were similar in term of gender (p=0.859), age (=0.071), type of first-line treatment (p=0.227), and performance status (p=0.150). With a median follow-up of 31 months (m), mortality rate was 41.2% and 70% in the ReRT and Bev groups, respectively. In the Bev and ReRT groups, median OS was 27 m (95% confidence interval (CI) 20-33.9 m) vs. 132 m (95% CI 52.9-211 m) (p<0.0001), median first-line PFS was 11 m (95% CI 7.14-28.7 m) vs. 37 m (95% CI 8.42-65.75 m) (p<0.0001), and median second-line PFS was 7 m (95% CI 3.9-10 m) vs. 9 m (95% CI 5.5-12.4 m) (p=0.564), respectively. CONCLUSION: The PFS is similar after the second line treatment of recurrent primary central nervous system malignancies either by re-irradiation or bevacizumab-based chemotherapy.

Associations between RORγt and T-bet Expressions, clinicopathological indices and survival rate in oral Squamous cell carcinoma patients.

BACKGROUND: Oral cancers are the sixth most common cancers around the world. According to the pivotal role of immune cells in the pathogenesis of oral squamous cell carcinoma (OSCC), as the frequent form of malignant epithelial neoplasm in the oral cavity, we investigated the association between the expression of RORγt and T-bet genes as two transcription factors, clinicopathologic indices, and survival rate. METHODS AND MATERIALS: Forty-two OSCC paraffin embded-blocks tissue samples and their surgical healthy margins (as a control group) were collected. Demographic information like age and gender, and medical history including tumor stage/grade, and following-up time were registered. The RORγt and T-bet expression were assessed by qPCR. The overall survival (OS) and disease free survival (DFS) were analyzed by SPSS V.23 software. RESULTS: The expression of RORγt and T-bet genes in OSCC patients were significantly higher than in surgical healthy margins (P < 0.001). Both expression demonstrated a significant difference between surgical healthy margins and tumor tissues related to gender and clinicopathological indices including stage and grade (P < 0.05). The expression of both genes in stage I patients was significant compared to stage IV (P < 0.05). The relation between expressions, OS, and DFS with clinical stage and histological grade of tumors was not statistically significant (P > 0.05). CONCLUSION: Overexpression of RORγt and T-bet in OSCC patients with higher grade and stage in compare to surgical healthy margin highlighted their critical role in OSCC pathogenesis including oral epithelial cell differentiation, tumorigenesis process, and malignant transformation. Moreover, both mentioned genes can apply as prognostic biomarkers in OSCC patients. We suggest surgical healthy margin be considered as valuable biological area.

Association between Tissue Expression of Toll-Like Receptor and Some Clinicopathological Indices in Oral Squamous Cell Carcinoma.

Background: The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)+ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC. Methods: Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient's disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software. Results: The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007). Conclusion: Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.

Case series on patients with primary central nervous system lymphoma: From clinical presentations to outcomes.

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma. In this report, we present 11 cases of PCNSL which were treated with high-dose MTX and WBI with a localized radiation boost to the tumor bed.

Post-neoadjuvant chemoradiotherapy tumor resectability following induction chemotherapy in locally advanced proximal gastric and adenocarcinoma of the esophagogastric junction: A clinical trial.

BACKGROUND: Pre-operative chemoradiotherapy (NACRT) of patients with proximal gastric and esophagogastric junction (EGJ) adenocarcinoma may result in increased local control and improved patients' survival rate. This study aimed to investigate the effect of NACRT on resectability of tumor in patients with proximal gastric and EGJ adenocarcinoma. METHODS: In this single-arm clinical trial, patients with locally advanced proximal gastric and EGJ adenocarcinoma were included. Two courses of paclitaxel/carboplatin chemotherapy alone followed by NACRT with a similar treatment regimen and a total radiation dose of 45-50.4/1.8-2 Grays were prescribed. After surgery, patients were evaluated for resection rate, pathologic response rate, and post-surgical complications. RESULTS: A total of 61 patients with a mean age of 65.9 years participated. Grades 1 and 2 were the most prevalent side effects, with grade 3 being the worst grade and exhibiting as leukopenia (4.9%) and thrombocytopenia (1.6%). 25 (41%) patients underwent surgery after NACRT. Post-surgery complication was reported in 20% of cases (including 8% mortality and 12% morbidity). R0 and R2 resection was observed in 88% and 12% of cases, respectively. Complete pathologic-response was achieved in 24% of patients. CONCLUSION: Paclitaxel/carboplatin based neoadjuvant chemotherapy was associated with potential resectability and appropriate pathologic response in patients with locally advanced proximal gastric and EGJ adenocarcinoma. However, by reducing patient tolerance to complete courses of weekly chemotherapy, induction chemotherapy lowered the effectiveness of concurrent chemotherapy and radiotherapy (as a sensitizing agent). Hence, induction chemotherapy proved to be more unbeneficial causing delayed treatment and reducing concurrent chemoradiotherapy tolerance.

Evaluation of the Relationship Between the Invasive Front of Oral Squamous Cell Carcinoma and Clinicopathological Parameters.

BACKGROUND & OBJECTIVE: The present study investigated the relationship between invasive front (IF) of tumors and clinicopathological parameters including stage, grade, nodal involvement, lymphocytic host response (LHR), recurrence, overall survival (OS), and disease-free survival (DFS). METHODS: A total of 87 oral squamous cell carcinoma (OSCC) biopsies were evaluated. Clinical stage, grading, nodal involvement, time of recurrence, OS, and DFS were assessed. The number of tumor budding cells in the IF was measured by two pathologists with an optic microscope. IF was graded to low risk (<5) and high risk (>5), according to the counting of tumor budding as a single cancer cell or cluster cells. Also, LHR was reported in the IF as mild, moderate, and severe. RESULTS: IF was reported in 43.7% of patients as a low-risk group and 49.4% as a high-risk group. LHR was also mild in 31%, moderate in 25.3%, and severe in 43.7% of the patients. Most of the patients were in stage IV (31%) and grade 1 (60.9%). The high risk IF group had a significant statistical relationship with stage (P=0.001), grade (P=0.039), five years OS (P=0.03), five years DSF (P=0.01), and lymph node involvement (P=0.007). The relation between LHR and stage of disease was significant (P=0.034). CONCLUSION: Considering the essential role of histopathological reports in the treatment plan of patients and the relationship between IF and clinical parameters, IF evaluation in routine histopathological examinations, especially in the early stages of OSCC, seems to be necessary.

Expression and Prognostic Significance of Cancer/Testis Antigens, MAGE-E1, GAGE, and SOX-6, in Glioblastoma: An Immunohistochemistry Evaluation.

BACKGROUND & OBJECTIVE: Glioblastoma is the most common primary malignancy of the brain, the prognosis of which is poor. Immunotherapy with cancer/testis (CT) antigens is a novel therapeutic approach for glioblastoma. This study aimed to investigate the expression rate of MAGE-E1, GAGE, and SOX-6 in glioblastoma tumors using the method of immunohistochemistry (IHC). METHODS: Expression of MAGE-E1, GAGE, and SOX-6 were determined by IHC in 50 paraffin blocks of glioblastoma. The results were compared between variables including age, gender, tumor location, and Karnofsky performance status (Kps) score. Survival analysis was also performed. RESULTS: The expression levels of SOX-6, MAGE-E1, and GAGE were 82%, 78%, and 76%, respectively. The relationship between CT antigens and age, gender, and tumor location was not significant, while the association between MAGE-E1 expression and age was statistically significant (P=0.002). High expression levels of SOX-6 and MAGE-E1 were associated with low Kps scores (P=0.034 and P<0.001, respectively). Survival analysis showed that age >40 and Kps score <80 were associated with significant relationship with shorter survival rate. (P=0.005 and P=0.018, respectively). Expression of MAGE-E1 and GAGE was negatively associated with overall 2-year survival rate (P=0.001 and P=0.021, respectively). CONCLUSION: The expression of all the three CT antigens, especially MAGE-E1 and SOX-6, was high in patients with glioblastoma. It can be concluded that these markers could be ideal targets for immunotherapy in such patients. MAGE-E1 and SOX-6 can be considered as important markers in determining the prognosis of glioblastoma.

Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement.

AIMS: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams. MATERIALS AND METHODS: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system. RESULTS: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2. CONCLUSIONS: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.

A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite of extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661, and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that the patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced overall survival (OS) of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5 ± 8.9 months vs. CG+GG: 47.7 ± 5.9 months; p value = 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of patients with ESCC. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC.

Primary duodenal malignant melanoma: A case report.

BACKGROUND: Melanoma is a neoplasm derived commonly from melanocytic cells of skin. Although coetaneous presentation of malignant melanoma is easily recognizable, the presentation of melanoma in other organs is so confusing. In particular, when it metastasizes to other organs, many bizarre figures and unusual organs may be involved. In this report, we present a case of primary duodenal malignant melanoma. CASE PRESENTATION: A 68-year-old man presented with a history of iron deficiency anemia. The upper gastrointestinal endoscopy showed a prominent papilla of duodenum along with an ulcerative lesion adjacent to second part of duodenum. Histopathologic evaluation showed a high-grade malignant neoplasm involving the bowel wall which was labeled for S100 protein and markers of melanocytic differentiation; Melan-A indicating the definitive diagnosis of malignant melanoma of the second portion of duodenal mucosa. CONCLUSIONS: In patients with a history of iron deficiency anemia, any GI symptom should be evaluated carefully. However, the diagnosis of primary GI melanomas in patients without any history of melanoma is possible. Full medical investigations are recommended in these patients with primary mucosal lesions.

A genetic polymorphism in the CYP1B1 gene in patients with squamous cell carcinoma of the esophagus: an Iranian Mashhad cohort study recruited over 10 years.

AIM: Esophageal cancer is the eighth most common cancer globally and the seventh most common cause of cancer-related deaths in men. Recent studies have shown that CYP450, family 1, subfamily B, polypeptide 1, which plays a role in the metabolism of xenobiotics, is associated with several cancers. Therefore, in the present study we investigated the association between a genetic variant, CYP1B1-rs1056836 gene, with the clinical characteristics of patients with squamous cell carcinoma of the esophagus (ESCC). METHOD: In this study, 117 patients with ESCC and 208 healthy controls were recruited. DNA was extracted and genotyped using real-time PCR-based TaqMan. Kaplan-Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between clinicopathological data, genotypic frequencies, disease prognosis and survival, Pearson's χ2 and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. RESULTS: The genotypic frequency for GG, GC and CC were 58.6, 29.8 and 11.5%, respectively, in the healthy subjects and 51.8, 36.14 and 12% in the ESCC group. An association between the GG genotype and stage of ESCC was found. Also, statistically significant results were not found for this variation and risk of ESCC. CONCLUSION: Our findings suggest a relationship between the CYP1B1-rs1056836 genetic polymorphism and clinical features of ESCC, supporting further studies in larger populations in different ethnic groups, taking into account potentially important environmental factors such as diet.