Middle East Journal of Cancer
Volume:14 Issue: 3, Jul 2023

Cancer is a disease in which molecular changes of the growth factors and relevant signaling cause uncontrolled growth and division of cells. The most common factors involved in cancer initiation and development include epidermal growth factor, mitogen-activated protein kinase, and autophagy effectors.
This experimental study was conducted to investigate the potential anticancer properties of a number of agents, including interferon-gamma, rapamycin, and vitamin B17, which were compared to Sorafenib in hepatocellular carcinoma HepG2 cell line and stem cells. Cells were cultured in RPMI medium with 10% fetal bovine serum, 4 mM sodium pyruvate, 4 mM L-glutamine, and 100 U/mL penicillin/streptomycin. Cell viability and levels of lactate dehydrogenase were investigated for the cytotoxic potential of these agents in both kinds of cells. The expression profile of Raf-1, autophagy-related LC3B, TP53, caspase 3 (Casp3), and levels of released inflammatory cytokines, including IL-4 and IL-6, were monitored in response to the chemical treatment.
Our findings showed insufficient inhibition of the indicated factors by interferon-gamma (IFN-γ) and rapamycin in cancer cells when compared to Sorafenib. Interestingly, vitamin B17 revealed competitive inhibition on cell proliferation of HepG2 cells compared with Sorafenib while in stem cells, vitamin B17 led to impartial consequences. Unlike TP53 and Casp3, gene expressions of Raf-1 and LC3B were significantly reduced in cancer cells treated with vitamin B17 at both RNA and protein levels, while their expression was markedly upregulated in the treated stem cells. Furthermore, in both cells, vitamin B17 increased the expression of IL-4 while reducing the production of IL-6.
These data provide evidence for the effectiveness of vitamin B17 in cancer treatment via selective regulation of Raf-1 and autophagy-related LC3B in cancer cells.

Carob (Ceratonia siliqua L.) has been used to cure various diseases in traditional medicine. This plant has also exerted antiproliferative effects on certain cancer types. The present study aimed to determine the effects of carob bean extracts on proliferation and apoptotic genes (Bax, Bcl-2, and P53) and Caspase-3, -8, and -9 expressions of human prostate cancer cell lines. In this in vitro experimental study, human prostate cell lines (LNCaP and PC3) were treated with carob bean extract (0, 50, 100, 200, 400, and 800 μg/ml) for 24, 48, 72, and 96 h. Cell viability was investigated via MTT assay. The genes expression: Bax (pro-apoptotic), Bcl-2 (anti-apoptotic), Caspase-3 (required enzyme for the execution of apoptosis), Caspase-8 (mediator of the extrinsic pathway), and Caspase-9 (mediator of the intrinsic pathway) genes, as well as P53 (tumor suppressor), were assessed using real-time polymerase chain reaction. Moreover, the nitric oxide in culture media was evaluated. Carob bean extract suppressed the proliferation of prostate cancer cells in a time and dose-dependent manner by inducing intrinsic apoptotic pathways and decreasing nitric oxide production (P < 0.01). The obtained results revealed the overexpression of Caspases-3 and -9, P53, and Bax, but reduction in Bcl-2 expression, giving rise to a higher Bax/Bcl-2 ratio (P < 0.05). The carob bean extracts exerted anti-prostate cancer properties via induction of apoptosis. It could be also suggested as a dietary supplement for patients suffering from prostate cancer.

Bladder cancer (BC) is known as the most frequent neoplasm of the urinary system, whose prevalence has significantly increased over the past three decades. Successful treatment of BC is a highly challenging task. In this regard, several studies have demonstrated that increased level of oxidative stress may cause cancer cells death. Furthermore, silver nanoparticles (AgNPs) are recognized as one of the most widely used nanomaterials in cancer treatment. Herein, we evaluated the AgNPs-induced oxidative stress in BC 5637 cell line.
In the current experimental study, using colorimetric reactions, we assessed the levels of oxidative stress parameters, including malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), as well as the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) as antioxidant enzymes. Moreover, we performed the statistical analysis via One-way ANOVA and post-hoc Tukey tests to draw comparisons between the groups.
The results indicated an increased amount of TOS, MDA, and oxidative stress index. Nonetheless, there was a remarkable reduction in SOD, GPx, and CAT activities and TAC level in the AgNPs-exposed cells compared to the control untreated ones (P < 0.05).
All in all, AgNPs have the potential to induce oxidative stress in 5637 cells. We thus concluded that AgNPs can be chosen as an antitumor agent for future investigations to treat BC.

Allogenic hematopoietic stem cell transplantation is considered as an effective treatment for patients with acute myeloid leukemia. However, complications of transplantation, like aGVHD, affect the efficiency of allogenic hematopoietic stem cell transplantation. The present study aimed to implement different models of data mining (DM) (single and ensemble) for prediction of allogenic hematopoietic stem cell transplantation in patients with acute myeloid leukemia (transplantation against host disease). We conducted this developmental study on 94 patients with 34 attributes in Taleghani Hospital, Tehran, Iran, during 2009–2017. In this practical study, data were analyzed via decision tree (DT) algorithms, including decision tree, random forest and gradient boosting (ensemble learning), artificial neural network (Single Learning), and support vector machine. Some criteria, like specificity, accuracy, Fmeasure, AUC (area under curve), and sensitivity, were reported in order to evaluate DT algorithms. There were 34 transplantation-related variables; some predictors, such as liver, hemoglobin, and donor blood group, were found to be the most important ones. To predict aGVHD, the two selected algorithms included the most appropriate DM models, artificial neural network and support vector machine classifiers, with ROC of 100. This study indicated that DT algorithms could be successfully used for approving the efficiency of the models predicting allogenic hematopoietic stem cell transplantation.

Apoptosis and autophagy functions are known as death-inducing mechanisms. Vincristine (VCR) is a chemotherapeutic drug that binds with tubulin dimers and induces apoptosis in cancer cells. Furthermore, VCR protects cancer cells from apoptosis, allowing them to enter autophagy. This makes cancer even more aggressive in its latter stages. Herein, we aimed to investigate the effect of VCR on autophagy and apoptosis in gastric cancer AGS and MKN45 cells under hypoxic conditions. In this experimental approach, we performed cell culture, cell viability analysis, ribonucleic acid (RNA) isolation, cDNA synthesis, and observation of gene expression levels. Subsequently, the amount of acidic vesicular organelles was investigated with acridine orange staining. Through the use of quantitative real-time polymerase chain reaction, we studied the effect of hypoxia and VCR on mRNA levels of hypoxia-related vascular endothelium growth factor(VEGF) and hypoxia inducible factor-1a (HIF-1α), as well as apoptosis-related Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2), and autophagy-related Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3-II) on AGS and MKN45 cell lines. The optimum VCR concentration was selected via cell viability analysis. The optimum VCR concentration was selected as 300 nM. VEGF, HIF- 1α, Bax, Bcl-2, and LC3-II mRNA expressions increased by 7.63, 3.34, 2.07, 4.09, and 3.1 folds, respectively, after VCR application to AGS cells under hypoxic conditions compared to the control cells. In MKN45 cells, Bax and LC3-II gene expressions increased by 5.21 and 12.2 folds, respectively, under the same conditions. In addition, the increase in the expression of autophagic LC3-II gene was consistent with acidic vesicular organelle formation. It was observed that VCR affects hypoxic, apoptotic, and autophagic gene expressions in AGS and MKN45 cells under hypoxic conditions.

Long noncoding RNA (lncRNA) is recognized as an essential controller of gene expression and other activities of the cells. Additionally, lncRNAs have a critical role in the progression and growth of human malignancies, like melanoma. Among lncRNAs, thymopoietin (TMPO)-antisense RNA 1 (TMPO AS- 1) has a significant role in melanoma. The current study aimed to determine the expression level of TMPO AS-1 in melanoma patients. In this case-control research, 50 pairs of tumor and non-tumor tissues of melanoma patients were separated by the surgeon. Subsequently, TMPO AS-1 expression level in the tissues was evaluated. We used TRIzol to extract total RNA from the tumor and non-tumor tissues, following which complementary DNA was synthesized. The TMPO AS-1 expression level of TMPO AS-1 was evaluated via quantitative reverse transcription- polymerase chain reaction (qRT-PCR) technique. Moreover, clinicopathological features of the melanoma patients were evaluated. Our findings revealed that TMPO AS-1 expression level was upregulated in the melanoma tissues in comparison with the non-tumor ones. Remarkably, the TMPO AS-1 expression level was considerably correlated to the clinicopathological characteristics of the patients, including lymph nodes and distant metastasis. Upregulation of TMPO AS-1 in melanoma indicated that TMPO AS- 1 and its downstream signal pathways could be used as a new target treatment option and prognostic tumor marker for melanoma.

Cancer has become a significant health challenge in recent decades. The Taxane family is one of the popular chemotherapeutic agents which can cause hepatic injury. The present study was conducted with the aim of evaluating the hepatoprotective effect of Curcumin on cancer patients treated with Taxanes.
This controlled randomized clinical trial (RCT) has been conducted on 80 patients with either breast, ovary, or pancreas cancer randomly allocated to the intervention group (n = 37) treated with daily 47.5 mg Curcumin extract or the control group (n = 34) treated with placebo. Hepatic indices, including alanine transaminase, aspartate transaminase, total bilirubin, and alkaline phosphatase, were measured and compared at baseline within three and six weeks after the intervention initiation.
The assessments revealed a remarkable increase in all of the indices in both groups by the time (P < 0.05), while these increases were remarkably less among the patients treated with curcumin in comparison with placebo treatment (P < 0.05). The Mean ± standard deviation was 26.3 ± 8.6 and 29.8 ± 10.5 for aspartate transaminase, 25.5 ± 8.3 and 30.2 ± 10.6 for alanine transaminase, 122.9 ± 18.02 and 126.8 ± 16.9 for alkaline phosphatase, 0.88 ± 0.10 and 0.95 ± 0.12 for bilirubin in the intervention and control groups, respectively.
Based on the current study's findings, Curcumin could act relatively as a hepatoprotective agent against Taxane; however, further studies are strongly recommended to determine the dosage and consumption instruction of this agent for patients with cancer.

Cervical cancer is characterized by the unusual growth of cells in the cervix. It accounts for about 25% of deaths in India; due to lack of knowledge, poor practice, and a negative attitude, diagnosis tends to arise at later stages of the disease. The main objective of our study was to evaluate cervical cancer knowledge, attitude, and practice (KAP) and to assess the relationship between educational status with knowledge and attitude toward cervical cancer. An online survey-based cross-sectional study was conducted among Indian women using a self-generated questionnaire for a period of six months. Cervical cancer awareness measure (C-CAM) was used to assess the knowledge. We recruited a total of 660 women aged 18 years and above. The majority of the participants had poor knowledge, strong positive attitudes, and poor practice. Among them, only 86 women were found to be vaccinated for HPV. A statistically significant association was found between the level of KAP of cervical cancer (P < 0.001). There was a significant positive correlation between KAP of cervical cancer. Our study concluded that the level of awareness regarding the screening techniques and preventive measures for cervical cancer is very low. Educational status had a significant association with KAP of cervical cancer. Hence, these outcomes suggest the need for more effective awareness-boosting programmes about cervical cancer screening. Promotion of free regular health check-ups and vaccination for cervical cancer among the general population will increase the awareness while decreasing the disease burden.

Gastric cancer is one of the most prevalent ones with high incidence and mortality worldwide. The aim of this study was to determine the serum levels of tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) as potential diagnostic biomarkers in the first-degree relatives of patients with gastric cancer.
The present work is a case-control study (case, n = 90; control, n = 90). The cases were selected from the first-degree relatives of the gastric cancer patients referred to Kosar Hospital of Semnan city, Iran, during 2019, consecutively. The controls were; however, a random sample from all the healthy people referred to Blood Transfusion Center of Semnan city in the same year. Demographic, laboratory, and pathological variables were collected from both groups. The levels of IL-6 and TNF-α were measured with ELISA method via platinum ELISA-8-11 kits. STATA 14 software was used for data analysis.
In the case and control groups, 74.44 and 78.79% were male, respectively. Their mean age (SD) was 39.17 (10.75) and 36.16 (10.19) in the case and control groups, respectively. Based on the multivariable logistic regression model, there was a statistically significant difference between the two groups in terms of TNF-α (OR = 1.15; 95% confidence interval (CI): 1.02 – 1.30) and smoking (odds ratio (OR) = 3.57; 95% CI: 1.48 – 8.64). However, no statistically significant difference was seen between them concerning the level of IL-6 (OR = 1.0004; 95% CI: 0.97 – 1.03).
Increased levels of TNF-α might be useful as diagnostic biomarkers in the first-degree relatives of patients with gastric cancer; nonetheless, studies with larger sample size are required.

Small cell lung cancer (SCLC) is known to be an aggressive cancer with poor prognosis. Prognostic factors are essential for the prediction of treatment outcomes and survival. The present study aimed to evaluate the prognostic value of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FFDG- PET/CT) in patients with SCLC.
In this retrospective study, the medical records of 41 patients with SCLC were reviewed; these patients underwent pretreatment FDG-PET/CT and presented to our institution from January 2012 to December 2017. PET/CT parameters, clinical factors, treatment, and follow-up data were collected and correlated to the overall survival (OS).
The median age of the patients was 61 years, only five of whom (12.2%) were female. Additionally, 29 patients (70.7%) were smokers, 9 (22%) were ex-smokers, and 3 (7.3%) were non-smokers. Among our subjects, 13 (31.7%) had limited stage disease, while 28 (68.3%) presented with extensive stage disease. The median pretreatment maximum standardized uptake value (SUVmax) for the primary tumor was 14.54. The median OS was 18.1 months. Based on univariate analysis, SUVmax, stage, age, and sex were significantly associated with OS. However, smoking status, tumor side, and lobe location had no significant impact on OS. Furthermore, according to multivariate analysis, SUVmax, stage, and age were independent prognostic factors for OS.
SUVmax, age, and tumor stage were found to be significant prognostic factors for OS in patients with SCLC.

Ovarian cancer is the most prevalent gynecologic malignancy in Egypt. Although metastasis from ovarian cancer is common, there are still sites with rarely reported deposits as non-regional nodes, bone, and brain.
We retrospectively recruited a group of patients over a 7-year period from the data system of a cancer center. All the recruited patients suffered from a rare distant metastasis from ovarian cancer. We used statistical software (SPSS) for the analysis of the study results. Continuous variables were presented as mean and standard deviation, if normally distributed, or median and range when non-normally distributed. Independent samples t-test was utilized to compare parametric data, whereas nonparametric data were compared through the use of the Mann-Whitney U test. Categorical data were compared with Pearson's Chi-square test or Fischer-Exact test when appropriate. A P-value < 0.05 was considered to be statistically significant.
Nearly half of the patients already had metastasis at the time of the initial presentation, while the rest developed it during the disease course. Debulking was feasible in nearly half of the patients with long overall and progression-free survival. Tumors with non-regional nodal metastases seemed to have excellent survival.
We could recommend offering these patients optimal debulking and considering those with a non-regional nodal spread as having a curable disease.

Despite its scarcity, malignant tumor extending to the heart is a lethal condition. Cardiac metastases are considered to occur rarely. In the present paper, we represented a single-center experience in cardiac metastases diagnosis in addition to different treatment modalities for improving the patients’ quality of life and survival. We could claim that this is the largest report of this kind to date. We retrospectively reviewed the patients’ files in our hospital, from 2009 to 2022. These patients presented with radiological/ intraoperative evidence of intracardiac extension of malignant tumor. Seven patients with transvenous intracardiac tumor extension were referred to our center. There was primary tumor in the lung in four cases (57.14%), two with synovial sarcoma (14.3%), one with renal cell carcinoma with inferior vena cava extension to the right atrium, and one with osteosarcoma. Moreover, there was one case of thymic origin (14.3%). Four patients underwent urgent surgery upon diagnosis, in order to have higher quality of life, and R0 resection which was not possible in any of them (two patients had R1 and two had R2). Among them, one received palliative chemotherapy followed by chemoradiation after debulking surgery, one received concurrent chemoradiotherapy, one received palliative chemotherapy only, and one refused to get any treatment. Survival was better in the patients who received concurrent chemoradiotherapy. According to our results, urgent/unplanned surgery could not be a good candidate for intracardiac extension of malignant tumors and does not improve survival. Combined multidisciplinary approach, on the other hand, was found to be a better option for disease control.

Folliculotropic mycosis fungoides (FMF) is a rare variant of cutaneous T-cell lymphoma which is categorized as a separate entity. In histopathology, malignant lymphocytes selectively surround and infiltrate hair follicles. FMF has different clinical features in comparison with classic MF which is more refractory to treatment and has a worse prognosis.In the current study, we describe a 42-year-old patient presenting as follicular papules with keratotic spines and alopecia on the scalp, face, and trunk. Histologic examination of the patient’s biopsy revealed follicular and perifollicular T lymphoid cell infiltration without follicular mucinosis. Clonality analysis was interpreted as CD4+ T cell lymphoproliferative disorder. With the final diagnosis of FMF, the patient underwent treatment with oral acitretin and topical corticosteroid and psoralen plus ultraviolet A (PUVA). This case, in addition to the accompanied review of literature, revealed the importance of considering FMF in spiny hyperkeratotic papules in seborrheic areas refractory to antifungal treatments.

Epithelioid rhabdomyosarcoma is an uncommon tumor. It is found mainly in somatic soft tissues like parotid, urinary bladder, trunk, neck, and limbs. Only two cases of this tumor in gastrointestinal tract (liver and gastro esophageal junction) has been reported to date; thus, we herein reported an unusual site of this tumor in the pylorus part of the stomach. In the present paper, we studied a 67-year-old male subject with complaint of dyspepsia, belching, and reflux for about 4 years. He had also consumed herbal drugs to relieve the pain for several years. In the endoscopy procedure, there was a large tumor at the distal part of the gaster. Furthermore, excisional biopsy was performed and the histological specimens showed tumor necrosis with high mitotic cell counts, large vesicles, eosinophilic cytoplasm of epithelial cells, and round nuclei. Immunohistochemistry staining was positive for Myogenin, Desmin, MyoD1 (30% ratio), and Ki67 (70 % ratio). Computed tomography scan images showed several metastases to peritoneum and lungs. After initiating the treatment, the adverse effects of chemotherapy persuade us to discontinue the regimen. Finally, the patient died due to pulmonary embolism. To conclude, primary epithelioid rhabdomyosarcoma is a very rare lethal cancer that may be found as gastrointestinal cancers. Hence, it requires further diagnostic investigations in order for the best treatment to be found.