Middle East Journal of Cancer
Volume:13 Issue: 4, Oct 2022

A high number of human breast cancers overexpress the murine double minute (MDM2) gene which blocks the p53 protein which plays an important role in arresting the cell growth. The present study aimed to investigate the efficacy of siRNA specific MDM2 in knocking down MDM2 and its subsequent effects on p53 to exert antiproliferative effects on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. In this in vitro study, we used the specific siRNA of the MDM2 gene to knock down the expression of the MDM2 protein in the MCF-7 cell line. The expression of MDM2, BCL2-associated X (BAX), BH3 interacting-domain death agonist (BID), and B cell lymphoma 2 (BCL2) genes was evaluated using the real-time polymerase chain reaction (PCR) technique. The apoptosis level was also assessed using the flow cytometry technique by the Annexin V test. The results showed that the entry of MDM2 siRNA into MCF-7 cells significantly reduced the mRNA expression of MDM2 gene (P-value < 0.05). Besides, the expression of the antiapoptotic gene of BCL2 significantly decreased (P-value < 0.05) in transfected MCF-7 cells, while that of BAX and BID genes increased (P-value < 0.05). Based on the results, MDM2 inhibition is conducive to prevent cancer metastasis by the induction of cancer cell apoptosis. Moreover, it can be considered in cancer therapy along with chemotherapy.

Acute myeloid leukemia (AML) is a complex disease characterized by clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure. Different genetic and environmental factors are believed to be involved in the pathogenesis of AML. Notch signaling with a tumor suppressing plays a role in myeloproliferative disorder and is a negative regulator of myeloid progenitor commitment. Crosstalk between Notch signaling and CXCR4 axis is a matter of debate in AML. In the current case-control study, we evaluated the expression level of CXCR4, JAG1, and MIB1, which are all involved or related to Notch signaling in adult AML patients. Blood samples were obtained from 25 AML and 17 healthy individuals and the expression level of the selected genes was evaluated via the real-time polymerase chain reaction. Our results revealed the increased expression of JAG1, but decreased expression of CXCR4 in AML patients in Iranian population of AML patients. Moreover, some gender-associated effects on the expression of JAG1 and CXCR4 were detected, which may be related to sex hormones. The expression level of MIB1 did not change significantly. The correlation analysis showed no correlations between the age of the patients and the expression levels of the genes. Herein, for the first time, we suggested some new evidence regarding the complex role of Notch signaling-related genes (CXCR4 and JAG1) in the pathogenesis of AML in Iranian patients.

Aldehyde dehydrogenase 1 (ALDH1) is an enzyme accountable for the detoxification of aldehydes. Sex-determining region Y-box 9 (SOX-9) plays a role in many biological and pathological processes. In this study, we aimed to evaluate the prognostic significance of ALDH1 and SOX9 expression in early breast cancer.
The expression of ALDH1 and SOX-9 was evaluated through immunohistochemistry derived from 50 eligible patients with early breast cancer included in the current prospective cohort study.
Positive expression of ALDH1 and SOX-9 were detected in 29 (58%) and 34 (68%) patients, respectively. The positive expressions of both markers were statistically significant associated with increasing the stage, lymph nodes metastasis, high Ki67 labeling index, and molecular subtypes (P < 0.001), along with with the biological markers; estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 over-expressions, and large tumor size (P = 0.039, P = 0.022, P = 0.024 and P = 0.003 for ALDH1 expression and P = 0.012, P = 0.007, P = 0.004 , and P = 0.002 for SOX-9 expression, respectively). There is a significant positive association between the expression of ALDH1 and SOX-9, r (correlation coefficient) = +0.806 (P < 0.001). Local recurrence was associated with the positive expression of ALDH1 only (P = 0.045) and the disease progression was statistically significant and associated with the positive expression of both ALDH1 and SOX-9 (P = 0.038, P = 0.023, respectively). There was significant association of positive expression of SOX-9 with reduced 3-y disease-free survival (P = 0.039).
Positive expression of ALDH-1 and SOX9 were associated with aggressive histopathological features and poor outcome in early breast cancer and can be considered potential prognostic markers in this group of patients.

Malignant melanoma is an aggressive skin cancer whose survival rate is extremely low. Commencing apoptosis is believed to be a significant issue in cancer treatment and targeting the apoptosis and WNT signaling pathways, which is probably a potentially successful strategy to overcome tumor plasticity in melanoma. We conducted the present in vitro study to investigate antiproliferative and apoptotic effects of Nic-ALA, as a new compound, on A375 melanoma cell line using MTT assay and flow cytometry, respectively. The gene expression profiles of the cancer cells were obtained for Bcl-2 and BAX as the main genes of the apoptosis signaling pathway and WIF1 and beta-catenin genes from the WNT signaling pathway with qRT-PCR. Nic-ALA’s cytotoxicity on A375 melanoma cell line from MTT assay was obtained with IC50 166.7, 144.2, and 146.1μM. This novel derivative induced 11.3, 46.1, and 85.7% of apoptosis in 24, 48, and 72h time points, respectively. In the treated cells, the expression of BAX, beta-catenin, and WIF1 genes increased, while the expression of Bcl-2 decreased significantly at 200μM concentration and the treated times of 48 and 72h. The antiproliferation of Nic-ALA at a lower value than what we found in nicotinic acid alone represented the higher bioavailability and transport efficiency of this novel derivative through A375 melanoma cell line. Its antipoetic effects were obtained by increasing the apoptosis rate and expression of the Bax gene and reducing Bcl-2 gene expression. Upregulation of WIF1 and beta-catenin in the WNT signaling pathway emphasized Nic-ALA’s anticancer effect on A375 melanoma cell line.

Radiation dermatitis is known to be a major side-effect occurring following cancer treatment. We conducted the present study to understand whether salivary lactate dehydrogenase (LDH) could be conducive to predict the development of radiation-dermatitis in the head and neck cancer (HNC) patients undergoing curative radiotherapy (60-70 Gy). This was a prospective study performed on HNC patients requiring curative radiotherapy. Saliva was collected at two points from the willing volunteers. The first time point was prior to the first fraction of 2 Gy radiation and the second one was 24 hours after the first fraction and before exposure to the second fraction. The saliva collected at the both time points were analyzed for the levels of salivary LDH using standard procedure. The patients were provided with the standard care throughout the treatment period and the incidence and severity of radiation dermatitis was noted down using a proforma sheet throughout the 7-week treatment period. The results suggested that with exposure to 2 Gy fraction, there was an increase in the level of salivary LDH (387.11 ± 18.98 IU/L vs. 368. 13 ± 19.56IU/L); this increase was significant (t = 20.06 and P < 0.001). The LDH data was stratified based on the severity of dermatitis [mild (grades 1 and 2) vs. severe (grades 3 and 4)] in accordance to the Radiation Therapy Oncology Group/European Organization for Research and Treatment Cancer (RTOG) grading. The LDH values were subjected to Karl Pearson’s correlation analysis with the grade of dermatitis and the results indicated a P value of 0.019 and R value of 0.24. For the first time, our study revealed that salivary LDH could be a useful marker to understand the development of radiation-induced dermatitis in HNC patients undergoing curative radiotherapy. The most advantageous aspect herewith is that the collection of saliva does not require skilled people or special equipment; it cou ld be done at repeated intervals and without causing any invasive process.

Immune checkpoint inhibitors (ICIs), including antiprogrammed cell death receptor-1, antiprogrammed cell death ligand-1, and anticytotoxic T-lymphocyte-antigen 4, have improved patients’ outcome in advanced malignancies. These agents are associated with immune-related adverse events, including skin toxicity, gastrointestinal toxicity, hepatotoxicity, renal toxicities, and endocrinopathies. We retrospectively reviewed the electronic medical records of patients treated with ICIs for advanced malignancies from two tertiary cancer care centers in the Emirate of Dubai, United Arab Emirates (UAE), including Dubai Hospital and American Hospital from November 2015 to January 2019. The patients were identified through the hospital cancer registry. We retrospectively collected data regarding the subjects’ demographics, cancer type, type of ICIs, thyroid-related adverse events, and duration of treatment. In the present paper, 43 patients received ICI and 19 (44%) developed thyroid dysfunctions. The median age of ICI-receiving subjects was 60 (27-80) years; 26 of them were male and 17 were female. Pembrolizumab was the most used agent (42%). Pretreatment thyroid functions were normal for all the patients. Following treatment initiation, 19 (44%) patients developed thyroid abnormalities, including overt hypothyroidism (n = 11, 57%), overt hyperthyroidism (n = 2, 11%), subclinical hypothyroidism (n = 4, 21%), and subclinical hyperthyroidism (n = 2, 11%). Thyroid abnormalities developed in 56% of them treated with Pembrolizumab and 37% treated with Nivolumab. Hypothyroidism was the most prevalent thyroid adverse event in the patients treated with ICIs in our study and the majority of thyroid dysfunction encounters took place in the first 6 weeks after ICI initiation. The treatment was well tolerated and there were no treatment-related discontinuations or deaths.

Breast cancer is one of the most prevalent types of cancer in Iranian women and the second cause of death in women worldwide. Gene mutations are the key determinants of the disease; therefore, the genetic study of this disease is of paramount importance. One of the genetic evaluation methods of this disease is microarray technology, which allows the examination of the simultaneous expression of thousands of genes. Clustering is the method for analyzing high-dimension data, which we used in the present research for collecting similar genes in separated clusters. A descriptive and inferential statistical analysis was carried out to evaluate unsupervised learning models of gene expression analysis and five bi-clustering methods (including PLAID (PL), Fabia, Bimax, Cheng & Church (CC), and Xmotif) were compared. For this purpose, we obtained the microarray gene expression data for lapatinib-resistant breast cancer cell lines from previously published research. The enrichment efficacy of the clusters was evaluated with gene ontology, and the results of these five models were compared with the Jaccard index, variance stability, least-square error, and goodness of fit indices. Furthermore, the results of the best model were assessed for building a genes sets network with Bayesian networks. After preprocessing, clustering was performed on the data with the dimension (4710 × 18) of the genes. Four models, except for CC, successfully found bi-clusters in the data set. The data evaluation revealed that the results of the models were almost the same, but the PL model performed better than the others, finding 11 bi-clusters; this model was used to build the network of gene sets. According to the results, the PL method was suitable for clustering the data. Accordingly, it could be recommended for data analysis. In addition, the gene sets network formed on gene expression data was incompetent.

Nipple-sparing mastectomy (NSM) is considered to be one of the most commonly used method of surgery in breast cancer. Oncologic and surgical complications are the major concerns associated with the NSM as a treatment or prophylactic approach for patients. The effective local control is the main goal in breast cancer treatment although aesthetic outcome and nipple-areola complex sensation are also important. This retrospective, descriptive, and cross-sectional study was performed on 35 hospitalized patients who underwent the NSM with axillary incision at the Department of Breast and Reconstructive Surgery at Sine Hospital, Tehran, Iran from April 2015 to April 2016. The patients were followed up in the first and second weeks and the first and third months following the surgery. 20 women who underwent the NSM were studied. The mean results in the flap sensation and in the nipple-areola complex sensation were 5.2 ± 2.4 and 5 ± 2.29, respectively. Major necrosis was reported in one patient in each follow-up session. Although acceptable necrosis rate and significant sensation recovery after this method of mastectomy makes it more accentuated, certain complications and necessary revision surgeries after the NSM may diminish the favorable results, including sensation.

Coronavirus disease 2019 (COVID-19) emerged in December 2019 in China and exhibited as a highly contagious viral infection which led to a high level of mortality and morbidity. It is followed by a great deal of complications, such as serious psychological disorders. There are a few studies evaluating the psychological status of COVID-19 on the patients with cancer in Iran. This was a cross-sectional study carried out on 94 patients with cancer who referred to Haft-e-Tir hospital for radiotherapy and chemotherapy from 20 April to 15 may, 2020. The data collection tool was the impact of events scale-revised (IES-R). The prevalence of anxiety disorders and obsessive compulsive disorder based on past psychiatric history in the patients was 11.7% and 2.1%, respectively. The results revealed that age was significantly related to avoidance dimension score (B = -0. 209, 95% CI: -0.084 to - 0.335). Regarding hyper arousal dimension score, the results were as follows: rural residency (B = 5.091, 95% CI: 0.610 to 9.573), past psychiatric history (PPH) (B = 8.312, 95% CI: 4.314 to 12.310), and radiotherapy (B = -2.976, 95% CI: -5.878 to -0.074) had a statistically significant relationship with the hyper arousal dimension score. The patients with cancer had a severe form of COVID-19. Individuals with cancer who had a previous psychiatric history are more vulnerable to post-traumatic stress disorder symptoms after trauma.

We evaluated the predictive factors associated with survival for gastric cancer patients with large tumor size (≥10 cm). In this retrospective study, we investigated 279 gastric cancer patients with large-sized tumors, treated at the Chonnam National University Hospital, Gwangju, Korea. We analyzed the clinicopathological features and predictive factors associated with survival in these gastric cancer patients with large tumors. Survival was calculated using the Kaplan-Meier method and the relative prognostic importance of the parameters was investigated through Cox's proportional hazards model. The recurrence rates were significantly different between the large and small tumor groups (76.3% and 36.6%, respectively; P < 0.001). Multivariate analysis showed that the presence of serosal invasion, nodal involvement, the extent of lymph node dissection, the presence of peritoneal dissemination, and curability had prognostic effects in gastric cancer patients with large-sized tumors. The 5-year survival rate was lower in patients with tumors ≥10 cm compared with those with smaller tumors (23.6% versus 57.0%, respectively; P < 0.0001). The 5-year survival rate was higher in patients with large tumor size who underwent curative resection (39.1%) than those who did not (10.0%) (P < 0.0001). The long-term survival of gastric cancer patients with large-sized tumors is related to curative resection. Thus, curative resection is of significance for predicting survival.

Long-term outcomes of intensity modulated radiotherapy with reduced high-risk clinical target volume (HRCTV) margin for radical chemoradiation of locally advanced head and neck cancers (LAHNSCC). The present retrospective study involved 83 LAHNSCC patients treated with chemoradiation. HRCTV was created with uniform margins of 5 mm around the primary tumor- gross tumor volume (GTV), and the nodal tumor GTV, edited at bone and air interface. The first echelon nodal station in N0 neck and that harboring disease in N+ neck was taken as intermediate-risk clinical target volume (IR-CTV). The remaining nodal stations were taken as low-risk CTV. High-, intermediate-, and low-risk regions were prescribed 70, 63, and 56 Gy, respectively, in 35 fractions, five to six fractions per week over six to seven weeks. 63 patients received five fractions and 20 patients received six fractions per week. Acute toxicities were assessed using CTCAE version 4.0 and the survival analysis was performed via Kaplan Meier method. Acute toxicities were grade 1 dermatitis in 77%, grade 3 mucositis in 35%, and xerostomia was predominantly grade 1 in 68.6%. Moreover, 10% required the placement of nasogastric tube during radiation therapy due to grade 3 dysphagia. Complete clinical and radiological response (CR) of respectively 89.1% and 85.5% was observed in primary and nodal disease at the end of the treatment and 100% and 94% at three months, respectively, after chemo radiation therapy. At a median follow-up of 48.1 months, the five-year overall survival was 63.2%. Reduced HRCTV margin of 5 mm was found to be efficient and had good compliance with tolerable acute toxicities, reduced overall treatment time, and reas onable long-term outcomes.

The current study aimed to determine the trends in esophageal cancer (EC) patients and examine the impact of the type and anatomical location of the tumor and the site of metastasis on their survival.

In this retrospective cohort study, we investigated 305 patients with a definite diagnoses of EC, who had been hospitalized at the Mahdie Hospital of Hamadan, Iran, during ten years from 2005-2015. EC-related survival considering different types and locations of the tumor, as well as the sites of metastasis, was evaluated. Survival was calculated using Kaplan-Meier curves and a multivariable Cox regression analysis (MVA) was performed.

Squamous cell carcinoma was found in 76.6% of the patients and 23.4% had adenocarcinoma (AC). There was a significant relationship between the location and pathological type of tumor; 87% of ACs happened in the lower part of the esophagus (P = 0.015). The 1- to 5-year relative survival of the patients was 46%, 25%, 22%, 12%, and 7%, respectively. The rate of death in liver, lung, brain, pancreas, abdomen, and lymph nodes metastasis were respectively 42.9%, 21.4%, 14.3%, 7.1%, 7.1%, and 7.1%. No significant relationships were observed between the tumor type and metastasis (P = 0.14) or between the tumor type and the location of metastasis (P = 0.7).

Similar to other reports, the rate of survival was higher in AC type, yet the rate of total survival in Iran was much lower than that in developed countries. There were no differences in the survival rate concerning the location of the tumor. The obtained results did not show any relationships among the tumor type, the location of metastasis, and the total survival.

Colorectal cancer is one of the most prevalent types of cancer in Iran. Detection and removal of polyps in colorectal cancer can significantly decrease the morbidity and mortality of the disease. The present study aimed to describe the characteristics of patients who had been detected with colorectal neoplasia.

This descriptive study was conducted on all the people who had been referred to the Research Institute for Gastroenterology and Liver Diseases for receiving colonoscopy services during 2017-2019. Information was collected through questionnaires designed based on four categories, namely personal information, clinical history, pharmacological history, and pathological results. We used logistic regression analysis to investigate the relationship between independent risk factors and colorectal neoplasia.

The total number of the patients referred to the hospital was 2826. The percentage of males was 43.06. There was a low statistically significant relationship between gender and having neoplasia (P = 0.053). We found that the history of diabetes was associated with neoplasia (P = 0.007). Watery diarrhea and abdominal pain had a relationship with colorectal neoplasia and P-values; they were both below 0.001. Moreover, weight loss and inflammatory bowel disease had a significant statistical relationship and P-values were 0.02 and <0.001, respectively.

In Iran, most colonic polyps are located in the left colon and also polyps that are situated in different locations. Our study could strongly suggest some important risk factors, such as age, smoking, and body mass index, whose impact on colorectal neoplasia has been reported by other papers.

The aim of this study was to determine pulmonary complications induced by radiotherapy and chemotherapy in patients with breast cancer in a six-month follow-up.

80 patients with breast cancer who were referred to the Radio-oncology Center in Kerman were included in the current cohort study.At the baseline, spirometry and lung scan were obtained and all the patients were asked about their respiratory symptoms. After designing the patient’s treatment, dose volume histogram data was extracted. All the tests were repeated six months after radiotherapy. The prevalence of pneumonitis and fibrosis in radiographs were determined clinically and the reduction in the values of pulmonary function test parameters was determined.

In 40% of the patients, pulmonary volume was reduced and in 10%, pulmonary fibrosis occurred. Regarding pulmonary function before and six months after radiotherapy, the results revealed that FeV1 (l/s) parameter decreased from 2.68 to 2.48 (P < 0.0001) six months after radiotherapy. FVC parameter also showed a decrease from 3.14 to 2.91 (P < 0.0001) in the same span of time. The odds of developing clinical symptoms in people with pulmonary fibrosis was five times higher than of those without this condition, (odds ratio: 5.51, 95% confidence interval: 1.10 - 27. 42), which was statistically significant (P = 0.03). None of the factors, including mean lung dose, tamoxifen, and age, affected Fev1 and pulmonary fibrosis.

Our results indicated that 10% of the patients undergoing treatment for breast cancer developed pulmonary fibrosis and 40% of the patients suffered from reduced pulmonary volumes, which was not associated with chemotherapy regimen or the use of tamoxifen.

Dosimetric comparison between 3D-conformal radiation therapy (3D-CRT) and helical tomotherapy (HT) in pediatric Medulloblastoma (MB) receiving craniospinal irradiation (CSI). This was a retrospective dosimetric study on five pediatric male patients diagnosed as MB, who were planned to receive CSI post-surgery. Treatment plans for 3D-CRT and HT were generated. Comparison was made in terms of planning target volume (PTV) coverage, homogeneity index (HI), conformity index (CI), organs at risk (OAR) dose, and treatment time (TT). HT increased the minimum dose up to PTV (81% vs. 74%) with better CI and HI (1.024 vs. 0.36 and 1.078 vs. 1.21, respectively). HT decreased the mean and maximum dose to OAR, except for higher mean dose of larynx, oral cavity, pharynx, and comparable V5 of lungs. TT of 3D CRT was shorter than HT (76 seconds vs. 545 seconds). HT was found to be a better treatment option in all the MB cases receiving CSI regarding PTV, conformity, homogeneity, and most of OAR, while TT was shorter in 3D-CRT plan.

Cancer diagnosis and treatments cause sexual dysfunction in patients. Sexual function is one of the most important aspects of quality of life. However, in previous studies, qualitative methods have been less accentuated to explore in to the sexual experiences and feelings of cancer patients. The aim of the present study was to investigate the experiences of Iranian women affected with cancer about their sexual quality of life. A qualitative descriptive study with a conventional content analysis approach was performed on a targeted sample of 28 Iranian women with cancer from October 2018 to February 2020. Data were collected through face to face and in depth semi structured interviews until data saturation was attained. Data analysis revealed four themes and 11 categories. The emerged themes were entitled: “Changing sexual capacity”, “physical consequences”, “sexual self-sacrifice” and “Changing woman’s identity”. Women with cancer experience many sexual problems such as reduced orgasm, lack of pleasure, and pain during sex. Due to the taboo of sexual issues, especially for women, many of them are embarrassed to ask their questions to the medical staff and for this reason, their problems will remain unresolved. The support of their spouses and the social can play an important role in facilitating coping. Health care providers have an important role in assessing and improving patients’ quality of life. It is recommended to adopt strategies for appropriate interventions, education and counseling to improve sexual quality of life in cancer patients.

Yolk sac tumors (YSTs) of the ovary are rare neoplasms, accounting for less than 0.2% of all ovarian tumors. Although this malignancy is much rarer in children, pediatric cases are attributed to a poorer prognosis. Diagnosis of YST is often made by post-operative pathologic examination. The prevalent clinical presentations include fever, distended abdomen or asymptomatic abdominal mass. YST rarely coexists with involvement of fallopian tube and this entity is rare in children.The present research was conducted to present a rare case of ovarian YST in an 8-month-old female infant with involvement of fallopian tube. This report, presents a rare case of YST in terms of its clinical presentation, histopathology findings, imaging findings, diagnosis, and treatment. The patient underwent surgical resection of the mass, followed by pathological examination, which confirmed an ovarian YST. To the best of our knowledge, this case is the youngest case of ovarian YST with the involvement of the fallopian tube reported in literature.

A 76-year-old woman presented with a one-year history of intermittent right lower abdominal pain, little weight loss, and palpable mass in the right lower quadrant of the abdomen. Pelvic ultrasound scan identified a lobulated hypo-hetero-echoic mass with some calcified foci. Computed tomography scan revealed a low-attenuated lesion-like mass in the perineal region, which suggested a cystic localized tumor. Colonoscopy showed sub-mucosal lesion in the cecum. The patient underwent laparotomy, and a right hemicolectomy (include ileum) with ileocolic anastomosis was performed. She was treated successfully. In the Histological examination, two mass-like lesions were found to attach to the appendix. In the proximal portion of the appendix, there were cystic structures that showed a low-grade appendiceal mucinous neoplasm. The tip of the appendix showed a well-differentiated neuroendocrine tumor (carcinoid tumor). In this unusual case, even though the initial origins of these two tumors are quite different, two tumors appeared in a single histological section.