Middle East Journal of Cancer
Volume:12 Issue: 4, Oct 2021

The AKT/PKB (protein kinase B) kinase is the main regulator of autophagy in mammalian cells, which consists of three isoforms, including AKT-1, AKT-2, and AKT-3. Rat sarcoma viral oncogene homolog (RAS), known as the most frequently mutated oncogene in colorectal cancers, is one of the major activators of AKT signaling. However, the relationship between AKT isoforms expression and autophagy level in RAS-driven cancer cells has not been fully investigated. In this experimental in vitro study, RAS mutated colon cancer cell lines (HCT116, SW480, and LS180) and HT29 cells, which are the wild type of RAS, were cultured and real-time polymerase chain reaction (RT-PCR) was utilized to determine the mRNA level of AKT-1, AKT-2, and autophagy markers, including microtubule-associated protein 1 light chain-3B (LC3B) and p62/sequestosome-1 (p62). In addition, Western blotting was performed to assess the protein expression of p62 and LC3B lipidation. We found that RAS mutated colon cancer cells up-regulate basal autophagy. Moreover, highly expressed AKT-1 was observed in RAS mutated colon cancer cells. However, no significant differences were found in AKT-2 expression between RASdriven cells and HT29 cells. Our obtained data suggested that RAS-driven colon cancer cells regulated the autophagy machinery, possibly, through the upregulation of AKT-1 isoform.

Cyrtopodion scabrum is a kind of lizard, widely distributed in southwestern, central, and eastern Iran. In our previous studies, we showed the selective anticancer properties of Cyrtopodion scabrum extract (CSE) against certain gastrointestinal cancer cell lines with no significant harmful effects on the normal cells.
This in vitro study was conducted to investigate the mechanism of action of CSE in SW742 (colon cancer cell line) using western blotting, real-time polymerase chain reaction (PCR), and PI staining/flow cytometry analysis.
Western blot analysis showed that CSE upregulates P53 protein expression significantly in SW742 cancer cell line, while QRT-PCR results revealed that P53 mRNA did not increase accordingly. It is proposed that TP53 protein play its role as a tumor suppressor through the protein stability mechanism and not through the increase in the gene expression. Considering this fact, for TP53 stabilization, two of its target genes, p21 and mdm2, were regulated. We evaluated the mRNA expression of these two genes as well. The obtained data showed a significant increase in both genes by CSE (1000 μg/ml), suggesting that the induction of G2 cell cycle arrest, which we previously reported, may happen through P53 and P21over-expression. No significant decrease was observed in apoptosis when SW742 cells were co-treated with CSE and the inhibitor of P53 transcriptional activity, (PFT)-α, indicating that the induction of apoptosis with CSE did not occur through P53-dependent transcriptional activity.
The obtained results herein revealed that the observed anticancer effect of CSE may occur through TP53 upregulation, yet with P53-independent transcriptional activity.

Human papillomavirus (HPV) positive head and neck squamous cell carcinoma (HNSCC) have distinctive molecular features. We conducted the present work to evaluate the HPV status of HNSCC patients and its association with expression of PIK3CA and CRNDE genes.
In the present case-control study, 50 fresh frozen tissue samples of HNSCC patients were collected from the patients referred to hospital for tumor removal. HPV typing was performed on DNA samples using a one-step polymerase chain reaction (PCR) followed by Reverse Line Blot method. Relative expression of PIK3CA and CRNDE genes was evaluated utilizing a real-time PCR method.
Out of 50 patients, 14 (28%) were HPV positive and the most prevalent type was HPV 16. Both PIK3CA and CRNDE genes were upregulated in tumoral tissues compared with adjacent non-cancerous tissues (ANCTs) (P=0.0322 and 0.0005, respectively). Based on the area under curve (AUC) values, the diagnostic power of CRNDE (AUC= 0.676) was higher than that of PIK3CA (AUC= 0.604). Finally, the expression level of PIK3CA was significantly associated with HPV+ HNSCC (P=0.01).
We showed that the prevalence of HPV in HNSCC was within our local prevalence range. Moreover, the association of PIK3CA overexpression with HPV status implied distinctive molecular characteristics of HPV(+) HNSCC.

The use of biomarkers has become increasingly important in the diagnosis and treatment of several malignancies, including breast cancer. Among the established biomarkers, receptor tyrosine-protein kinase erbB-2 (HER-2/ neu) has been found to be of a predictive and prognostic role in breast cancer patients.

94 patients with primary breast cancer were enrolled in our prospective study between 2016 and 2017. 5 cc clot blood samples were taken for serum HER- 2/neu testing at the time of diagnosis of breast cancer. The patients’ demographic data, tumor characteristics, including tumor size, tumor grade, presence of lymph node involvement, and stage, hormone receptor, and tissue HER-2/neu status of the subjects were recorded following tumor removal.

All of the patients were female with the age range of 27 to 80 years (the mean of age was 49.66. 36 patients (38.3%) had positive tissue HER-2 results and 58 (61.7%) had negative results. In those with high level serum HER-2 ECD, 28(77.7%) had positive tissue HER-2 and 8(22.2%) had negative results. Moreover, in the patients with low level serum HER-2 ECD, 8(13.7%) had positive tissue HER-2 and 50(86.2%) had negative results with the sensitivity of 77.7% and specificity of 86.2%. HER2 ECD levels were highly concordant with tissue HER2 status, with a P value of less than 0.001, which was considered to be statistically significant. Among different clinicopathologic variables, serum and tissue HER-2/nu were significantly correlated with only tumor grade.

A significantly increased release of HER2 ECD levels may accurately predict tumor HER2 status as detected with immunohistochemistry and/or in situ hybridizations studies.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the endocrine system. This study was aimed at evaluating the serum substance P (SP) levels, the tissue distribution of Neurokinin-1 receptors (NK1-R), and their possible diagnostic value in PTC.

The present case-control study included 31 healthy volunteers and 31 cases (age range: 25-64, 40.26 ±12.77), who were primarily diagnosed with PTC and were candidates for total thyroidectomy. Pre-operative serum level of SP was measured using a commercial ELISA kit. The tissue distribution of NK1-R was assessed immunohistochemically.

The serum level of SP in the patient group was higher than the healthy volunteers (P = 0.005). Besides, the expression of NK1-R was higher in tumoral tissues compared with their normal surroundings (P = 0.005). However, we observed no significant correlation between either SP level or NK1-R expression and the disease stage or lymph node involvement.

SP level and NK1-R expression were upregulated in PTC patients, showing the involvement of SP/NK1R complex in PTC pathophysiology. Nonetheless, proposing SP/NK1R as a diagnostic factor requires further studies because we found no correlation between SP/NK1R and clinical stage or lymph node involvement.

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer-related deaths worldwide. Egypt is one of the African countries with a high incidence of HCC. The process of carcinogenesis in the liver, particularly in post-hepatitic necrosis, is related to the severity of liver damage and fibrosis. The present study aimed to investigate the utility of King’s score to identify patients at higher risk of developing HCC among patients with hepatitis C virus-related cirrhosis. 58 patients were included in this retrospective case-control study. They were divided into two groups; group I included 29 patients diagnosed with HCC and group II comprised 29 patients without HCC. King’s score was calculated for all the patients based on their pararmeters at the time of diagnosis and their records of one year prior to the diagnosis. King’s score was significantly higher in group I, not only at the time of diagnosis (95.4±45.2 vs. 24.23±7.4, p <0.001), but also when calculated from the patients’ records a year before the diagnosis (70.4±41.8 vs. 17.46±8.2, p <0.001). King’s score can diagnose higher risk of developing HCC up to one year before the appearance of focal lesion.

We examined and estimated the trend of breast cancer incidence in Kerman, the largest province in Iran.

Having compiling the data of new cases from three sources (cancer registry, pathology, radiotherapy) in this longitudinal study, the number of untouched cases was estimated using log-linear model. We estimated the annual age-standardized rate (ASR) per 100,000 women in 2001-2015. We utilized joint point regression method to estimate the trend of breast cancer incidence during the examined years.

The ASR of breast cancer increased from 25 in 2001-2005 to 37 in 2011- 2015, showing that the annual average percentage increased by 5.9% (95% Confidence Interval: 3.5, 8.4, p <0.001). Moreover, during this period, the completeness of the cancer registry increased from 16% in the first five years to 70% in the last five years.

Our findings revealed that the coverage of the cancer registry increased significantly. It seems that part of the increasing trend of the reported cancer incidence was attributed to the enhancement of the cancer registry scheme, but our findings suggested that the real incidence of breast cancer had a growing trend.

The objective of this study was to compare the dosimetric outcome of plans with more fields to those with fewer ones for breast cancer patients. 23 breast cancer patients were examined in this experimental study. Two groups of these patients were planned by treatment planning system. The number of beams was changed for each group, and the dosimetric parameters were calculated. The dose volume histogram (DVH) and the statistical analyses were performed for the two plans of all patients. The DVH for the planning target volume (PTV) of the two techniques was estimated. Optimized plans were carried out to ensure that 95 % of the target volume takes 95 % of the dose. Based on the statistical analysis, the best coverage of dose had no relationship with the number of beams because the P-value of V105 %, V95%,V110%, Dmean, Dmax, conformity index, homogeneity index, and D5% were 0.9537, 0.9152, 0.3446, 0.8156, 0.9516, 0.7888, 0.2127, and 0.7282, respectively. The Mean ± standard error of mean for all PTV parameters was nearly the same. Also, the organ at risk had no significant difference after changing the number of beams, which means that the complication to normal tissue was nearly the same for both plans. The number of beams has no effect on PTV and normal tissue. Therefore, it is important for medical physicists to conduct the optimized plan without exceeding the number of beams to reduce the scattered radiation.

Concurrent chemo-radiation has proven to be beneficial in a majority of patients with locally advanced head and neck cancers. Despite modern techniques of radiation delivery, the trade-off is acute and entails late toxicities for a considerable number of patients. Very few studies have reported the outcomes of these patients. We aimed to prospectively assess and report the toxicities of patients undergoing definitive chemo-radiation by the volumetric modulated arc therapy (VMAT) for the treatment of advanced laryngeal and hypopharyngeal cancer. This prospective observational study was conducted in a single tertiary care center over a period of two years. We recorded acute and late toxicities during and after the treatment of patients with locally advanced laryngeal and hypopharyngeal cancer treated with definitive chemo-radiotherapy using VMAT. Chi square test and Fisher’s exact test were used for comparing the significance of outcome parameters with different variables. 28 patients who met the inclusion criteria were taken up for analysis. The median age was 59 years. The median treatment time was 48 days. The mean dose to parotid, superior, and mid constrictors was 32, 45, and 64 Grays (Gy). At completion, 7% of the patients had grade 3 or more dermatitis, 4% had grade 3 or higher mucositis, and no patient had grade 3 or higher xerostomia. Five patients treated for hypopharynx cancer developed strictures. Our results showed that concurrent chemo-radiotherapy using VMAT is a promising method of treatment for advanced laryngeal and hypopharyngeal squamous cell cancer with an acceptable toxicity profile.

Iran is a high-risk area with a poor prognosis for esophageal cancer. We conducted the present study to evaluate the survival rate of esophageal cancer after the introduction of neo-adjuvant chemo-radiation at the Cancer Institute of Iran.

We performed a retrospective cohort study and abstracted the data of 421 patients who referred to the Cancer Institute of Iran between 2007 and 2011. Life table and Kaplan-Meier approaches were applied to estimate 1-, 3-, and 5-year survival rates and corresponding 95% confidence intervals (CI). Multiple Cox regression model was recruited for investigating the association between 5-year survival rate and prognostic factors.

We found that 1-, 3-, and 5-year survival rates were 66.7%, 28.2, and 20.9%, respectively. The hazard ratio (HR) was significantly higher among the patients who has received definitive chemo-radiation therapy (Hazard ratio (HR) = 2.2, 95% confidence interval (CI): 1.1, 4.2), surgery (HR= 2.0 95% CI: 1.0, 3.7), and palliative care (HR= 4.2, 95% CI: 2.1, 1.8) compared with those who received neo-adjuvant chemo-radiation and surgery. We also found that the 5-year survival rate was doubled in the current study conducted between 2007 and 2011 (20.9%) compared with the previous one conducted between 1997 and 2006 (10.0%). Additionally, a considerable improvement was observed in 1- and 3-year survival rate of esophageal cancer at the Cancer Institute of Iran.

Following the administration of neo-adjuvant chemo-radiation therapy, the prognosis of esophageal cancer has improved significantly at the Cancer Institute of Iran during the last decade. More data from other cancer centers and provinces of Iran are required.

The impact of initiation time of radiotherapy after breast surgery on disease-free status of patient is a controversial issue. We assessed the relationship between the delay in adjuvant radiotherapy and surgery and relapse or metastasisfree survival in women with breast cancer taking heavy censoring into account.

This was a historical cohort study on 284 patients with breast cancer, who underwent surgery between 2001 and 2007 and followed up until March 2017. The association of the duration between radiotherapy and surgery, as well as other demographic and clinical factors with occurrence of local relapse or metastasis of breast cancer was examined through penalized Cox regression modeling. The obtained data were analyzed using R 3.6.3.

A total of 284 women with the mean age of 47.2 ± 11.3 years met the inclusion criteria. The maximum follow-up time was 11.1 years and the time between surgery and radiotherapy was 168 ± 84.3 days. About 10% of the patients experienced local relapse and 19% had metastasis. In multiple analysis of factors related to diseasefree survival, the stage of disease was significant, while surgery to radiotherapy interval (≤180 days vs >180 days) did not have any significant impact on hazard of failure. Analysis of 3, 4, or 5 months of delay in radiation therapy did not imply any significant affects.

In the studied patients, the delay in radiotherapy initiation after surgery did not lead into outcomes of local relapse or metastasis.

Quality assurance for intensity modulated radiation therapy (IMRT) depends on the type of dosimetry system and its evaluation procedure. We can check both the intensity and distribution of each field as the required pretreatment verification with dosimetry systems. Treatment verification for different plans (IMRT and RapidArc) applied on localized prostate cancer patients was done with electronic portal imager device (EPID), Delta4). The EPID used was Varian aS1000 mounted on Varian (TrueBeam) Linac with gamma criteria set to ΔD=3% and Δd=3mm. RapidArc plans were designed by arcs (179.0o CCW to 181.0o and 181.0o CW to 179.0o) under the same gamma criteria of (ΔD=3%, DTA=3mm and Δ-index ≤1), while the threshold dose was 20%. Evaluation analysis is passed for IMRT prostate plans with the area gamma 0.8 (was equal to 2.1%) / area gamma >1.2 (was equal to 0.3%) and the average dose difference was 0.42CU. Delta4 dosimetry system was assessed with RapidArc plan; the agreement between the measured and planned doses was ±1% and gamma analysis resulted in 100% data points with the same agreement conditions. Portal dosimetry provided a good verification of the treatment unit ability to deliver doses according to plan. For an IMRT field comprised of several subfields, it could give rise to much more errors. RapidArc plans were verified using Delta4 system, which generated excellent dosimetry results. Periodic calibration was recommended for Delta4 dosimetry system; radiation damage affected sensitivity by >1% every 1kGy.

We conducted the present study to assess the practice of breast selfexamination (BSE) among Debre Tabor University female undergraduate students, northcentral Ethiopia using health belief model (HBM). The current institution-based cross-sectional study was carried out among a total of 341 students. Simple random sampling technique was employed to select the study participants. We also used self-administered pretested questionnaires and constructs of HBM for collecting data. Binary and multivariable logistic regression were utilized to identify BSE-associated factors. Statistical significance was stated at P value < 0.05. Approximately 45% of the participants had a fair level of knowledge about breast cancer (BC), but only 17% were actually performing BSE practice. The odds of practicing BSE were found to be higher among the participants who had information about BSE practice adjusted odds ratio (AOR)=7.21, 95% confidence interval (CI): (2.46, 21.15)), perceived susceptibility (AOR=14.18, 95% CI:(4.00, 50.48)), self-efficacy (AOR=3.07, 95% CI: (1.09, 8.70)), cue to action (AOR=3.68,95% CI: (1.17, 11.56)), and net benefit (AOR=7.75, 95% CI: (1.56, 38.55)) compared with counterparts. Whereas, the odds of practicing BSE were found to be lower among those who had poor knowledge of BC (AOR=0.08, 95% CI: (0.03, 0.23)) compared with counterparts. In this study, knowledge regarding BC and BSE practice was observed to be low. Knowledge about BC, having information on BSE, perceived susceptibility, self-confidence, and cue to action were found to be independent predictors of BSE practice. Providing targeted information about BSE is the best method of changing the behavioral intention of university students about BC and BSE practice.

In the current study, we used the information-hierarchical system approach to examine human metabolism. Metabolism hierarchical structure, beginning from enzyme level, is controlled by the established information principle and divine section numbers. This structure represents a key mechanism of the hierarchical biological clock (HBC) of human body. Time cycles of HBC hierarchical levels are nested into each other according to strict dynamics schemes. The cycles form the HBC scales of 1, 6, 42 seconds, 24 hours (circadian rhythm), and 11 days and jointly make up the precision HBC similar to the conventional countdown (1 s, 1 m, 1 hr, 1 day, and 1 month). Diagnostic/prognostic studies of cancer require a detailed analysis of metabolic HBC disorders. We utilized the information-hierarchical system approach and the information principle in order to analyze HBC run under different dietary patterns. We characterized hierarchical metabolic systems with 24-hour and 11- day operation times. The 24-hour circadian rhythm comprised citrate, pentose, and fatty acid (anabolic or catabolic) biochemical cycles individually. The 11-day cyclicity referred to these cycles combined into a ternary system of the higher-rank hierarchical level. Disorder of systems operation should lead to a radical change in HBC run with subsequent transformation of normal cells into cancer cells. Mutations of metabolic enzyme genes can damage HBC run, thereby leading to cancer and other chronobiological disorders. Organized rhythmicity of external factors (everyday food intake, 11-day periodical dietary pattern, and so forth) made it possible to heal cancer cells per se. Applying a particular kind of diet, the human lifespan could significantly increase. The proposed direction of cancer prevention and treatment can be called a cancer metabolism chronotherapy.

Obesity is linked with a high risk of breast cancer and affects prognosis as it is correlated with different molecular subtypes. All breast cancer patients referred to Kasr Alainy Oncology Center of Clinical Oncology and Nuclear Medicine (NEMROCK) from 2004 to2014 were recruited in this retrospective study. They were divided into three groups according to body mass index (BMI): non-obese (BMI < 30), obese (BMI= 30-34.9) and severely obese (BMI ≥ 35). There were 950 breast cancer patients with a median follow-up of 4.2 years. The mean age was 50.1 years, and BMI was assessed in 760 cases. Obesity was observed in 63.29% of the cases (23.82% obese and 39.47% severely obese). There was a statistically significant difference between non-obese and severely obese patients as regards age (52 vs. 48 years, P < 0.001), menopausal status (31.3 vs. 46.9%, P < 0.001), molecular types (non- luminal; 25 vs. 50%, P < 0.011), Her2 status (44.4 vs. 27.2%, P = 0.014), and hormonal therapy (Tamoxifen alone, 44.3 vs. 30.4%, P = 0.001). High BMI >30 had a worse mean overall survival (OS) (80, 88, and 102.5 months in obese, severely obese, and non-obese patients, respectively, P=0.019); however, this did not affect the disease-free survival (P = 0.40). In multivariate analysis, the factors that also had a significant effect on OS were lymph node stage (P <0.001; odds ratio (OR): 1; 95% confidence interval (CI): 0.07-0.46), BMI (P = 0.001; odds ratio (OR): 1; 95% CI: 0.14-0.61), and hormonal treatment (tamoxifen alone, P = 0.001; OR: 1; 95% CI: 1.4-16.4). Severe obesity (BMI >35) had a poor OS with no influence on disease-free survival.

Ovarian yolk sac tumor in pregnancy is a very rare case (<5%). The management could be very challenging since studies regarding the disease are very limited. This case report is written in order to report a rare case of yolk sac tumor in pregnancy and its management.A 29-year-old woman with a 16 weeks gestational age (WGA) in her first pregnancy presented in the emergency room with severe lower abdominal pain. Next, she underwent exploratory laparotomy, and a biopsy was performed, which indicated an ovarian yolk sac tumor. The patient was then given neoadjuvant chemotherapy with carboplatin and paclitaxel. The pregnancy resulted in an intrauterine growth restriction (IUGR) baby, delivered on 33 WGA. The baby was delivered through C-section and the mother continued to undergo optimally debulked laparotomy, total hysterectomy, bilateral salphingo-oophorectomy, omentectomy, and rectosigmoid tumor resection.In dealing with a rare case with limited resources, tailor-made management is required. The most ideal treatment may not be performed, but the clinician should be more adaptive for the patient to have a better outcome.

Subcutaneous panniculitis-like t-cell lymphoma (SPTL) is known as a rare type of cutaneous lymphoma characterized with penetration of neoplastic T cells to the subcutaneous tissue. It constituates less than 1% of all non-Hodgkin lymphomas.
We described herein a 49-year-old woman with SPTL who presented with redpurple- colored persistent subcutaneous nodules disseminated on trunk and both extremities. The lesions were present for 15 years. She had been diagnosed as panniculitis and her lesions had not regressed with panniculitis treatment. SPTL was diagnosed due to histopathological examination of the lesions that revealed CD3 positive, CD8 positive, CD4 negative and CD56 negative atypical lymphoid infiltration with lobular and septal panniculitis-like pattern.
SPTL must be always kept in mind as a differential diagnosis, while examining biopsies of patients with panniculitis-like lesions resistant to long-term treatment. It is also important to remember that the biopsy material should be in such depth that involves subcutaneous fat tissue.

A 56-year-old female patient was presented with abdominal distension and decreased appetite. Diagnosis confirmed breast cancer, a mastectomy, and multiple lines of chemotherapy. Later on, the patient developed liver metastasis and received whole liver radiotherapy (WLRT) for diffuse liver metastasis. This phenomenon is still the most prevalent site of metastases, particularly in lung, breast, and gastrointestinal cancers owing to its rich, dual blood supply and its role as a filter in the portal circulation. Conventional treatment approaches are not effective in such patients due to diffuse liver involvement; thus, the use of low-dose WLRT is considered as a good alternative. In practice, palliative liver irradiation is a rare modality due to radiationinduced hepatitis. However, WLRT treatment aims at the palliation of symptoms and improving the patients’ quality of life rather than enhancing survival. Results of the present case report also showed that WLRT in patients with poor performance status would ultimately improve their palliative symptoms and overall quality of life with acceptable morbidity.

The patients with multiple malignancies are difficult to diagnose as one malignancy may be indolent and usually diagnosed as an incidental finding, while proceeding with staging work-up for the other malignancy. Treating such patients is even more difficult due to the issues related to sequencing the treatment for each of them. We report a case study where a patient was diagnosed with dual malignancies (Hodgkin’s lymphoma and adenocarcinoma lung) and was treated for both malignancies sequentially. The patient had five years of disease-free survival and was kept under follow-up. He was diagnosed with metachronous malignancy, squamous cell carcinoma of esophagus, and underwent treatment for the same condition.

Kimura disease is a rare entity causing subcutaneous swellings and lymphadenopathy, with hardly 120 cases reported worldwide. It is mainly seen in Asian men. Herein, we present a typical case that presents with submandibular mass and persistent eosinophilia. The patient was a 38-year-old man suffering from left submandibular mass for the last 5 years. It has happened upon a dental infection. Treatment with prednisolone resulted temporary decrease in the size of the lesion, but it wouldn't disappear totally. Since the swelling did not get improved, an excisional biopsy was conducted. The high rate of the eosinophil and histopathology results conducted us to diagnose him with Kimura.Histologically, Kimura disease presents as lymphadenopathy with preserved lymph node architecture and reactive and prominent germinal centers. Dense eosinophilic infiltration of the interfollicular zones, lysis of the follicles, and occasionally microabscesses are seen. Granuloma formations contain infiltration of eosinophils, lymphocytes, plasma cells, and histiocytes. Tissue fibrosis, sclerosis, and vascular proliferation are also present. Vessels remain thin-walled with cubical endothelial cells. This was in line with our patient symptoms.