Middle East Journal of Cancer
Volume:14 Issue: 2, Apr 2023

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer which is characterized by the absence of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2, thus, TNBC patient tumour does not respond to the endocrine therapy. TNBC is highly invasive, highly metastatic, and shows poor prognosis, recurrence, and short survival rate. Surgery, chemotherapy, and radiotherapy are now used as treatments. Despite the wide range of treatment choices, the main drawbacks of current therapies include drug resistance, decreased effectiveness, recurrence within 5 years, and a variety of side-effects. A unique targeted approach is therefore desperately required for the treatment of TNBC. Researchers now have fresh perspectives on the tailored strategy for treating TNBC thanks to phytochemicals. Phytochemicals have shown antiproliferative properties in TNBC and also overcome the drawbacks like recurrence, toxicity, adverse effect, and quality of life. This review highlights different phytochemicals and their potential to target signalling pathways and gene expression to induce apoptosis, cell cycle arrest, inhibition of metastasis, and angiogenesis.

Radiotherapy is a frequently used therapeutic modality for breast cancer. Dalbergin, a natural antioxidant, inhibits carcinogens and tumor progression. In the present study, we investigated the effect of Dalbergin on the response of T47D and MDA-MB-231 breast cancer cell lines to ionizing radiation. In this experimental in vitro study, doubling time of T47D and MDAMB- 231 were obtained from the growth curve. The cytotoxic effect of Dalbergin on T47D and MDA-MB-231 breast cancer cells were estimated via MTT assay. To determine the clonogenic ability, we treated T47D and MDA-MB-231 with Dalbergin for 48 h prior to irradiation, subsequent to which a colony assay was performed. Real-time polymerase chain reaction was employed to determine the gene expression level. Dalbergin inhibited proliferation of T47D and MDA-MB-231 in a time and concentration-dependent manner. Additionally, the most appropriate time for the treatment of these types of cancer cells was found to be 48 h and the drug's concentration in both cell lines was different. The IC50 values of T47D and MDA-MB-231 cells were 0.001 and 0.0001 μM, respectively. Moreover, this drug radiaosensitizes both cell lines effectively compared with the radiation only. Finally, the gene expression level of p53, Bcl-2, and STAT3 were investigated in cancer cells. Dalbergin showed apoptotic effects probably through the STAT/p53 signaling pathway. Therefore, Dalbergin could be considered as a radiosensitizer and its effects may be owing to increased cell death.

Myocardial infarction-associated transcript (MIAT) is a long noncoding RNA (lncRNA), which functions in a variety of disorders, like myocardial infarction and diabetic retinopathy. Moreover, recent reports have established that MIAT is upregulated in several types of malignancies and plays a crucial role in tumorigenesis. Therefore, this research aimed to investigate the expression of MIAT in colorectal cancer (CRC) and further evaluate the impact of its knocking-down on the proliferation and migration of the CRC cell. In this case-control experimental study, we evaluated the expression level of MIAT in a series of CRC and marginal tissues using RT-qPCR. Furthermore, the role of MIAT was assessed employing RNA interference (RNAi)-mediated suppressing strategy in CRC-derived cells. Subsequently, colony formation, cell cycle analysis, migration, apoptosis, and senescence assays were done to decipher the influence of MIAT on initiation and progression of CRC. Our findings revealed that MIAT expression is significantly upregulated in high-grade and vascular invasion tumor tissues. Furthermore, MIAT silencing led to G1 arrest in SW116 and SW48 CRC-derived cells. We also found that MIAT inhibition contributed to the induction of apoptosis/cellular senescence as well as the limitation of colony formation capability and cell migration in CRC cells. The obtained findings also showed that MIAT silencing dysregulated the expression of ATM and CHK2 genes known as DNA damage responsive genes. The results of the present study demonstrated that lncRNA MIAT may control CRC cell proliferation and metastasis through regulating DNA damageresponsive pathway and can be noticed as a potential marker for diagnosis, prognosis, and targeted-therapy of high-grade CRC.

Thymoquinone (TQ), an active part of Nigella sativa, has been reported as an anticancer agent. This study aimed to evaluate different anticancer effects of TQ on oxidative stress markers and Peroxiredoxin 4 (P4) in lung cancer A549 cell line.
In this experimental study, we used TQ concentrations to treat lung A549 cells and determined cell viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay at 12, 24, and 48 h times. The IC50 concentration of TQ was found with MTT assay. We studied the total antioxidant capacity (TAC) and total oxidant status (TOS) using the manual assay, and analyzed catalase (CAT), superoxide dismutases (SOD), and glutathione peroxidase (GPx) activity using the enzyme-linked immunoassay (ELISA) kits. Moreover, the concentration of peroxiredoxin-4 (PRXD4) was measured with the ELISA Kit.
The IC50 of TQ for A549 cells was calculated to be 40 μM concentration for 24 h of incubation. TAC index significantly decreased in the treated cells compared with the controls (P = 0.05), whereas TOS and PRXD4 levels showed a significant increase (P = 0.05). Additionally, the results showed that the CAT, SOD, and GPX activity enzymes significantly decreased in 20, 40, and 60 μM TQ in comparison with the control cells (P = 0.05).
TQ has significant inhibitory effects on A549 cells and could be utilized in novel therapy not only for lung cancer, but also for other tumors.

In this study, we aimed to investigate the combined effect of sodium valproate (SV) and lithium (Li) against viability, migration, and invasion of prostate cancer cell line. In this in vitro study, PC3 cells were treated with different concentrations of SV (2.5, 5.0, and 10 μM) and Li (2.5, 5.0, and 10 mM) either alone or in combination. Using the MTT test and annexin V/7ADD flow-cytometry, cell viability and apoptosis were assessed. Transwell chamber test was used to assess PC3 cells' invasion and migration. SV and Li alone had no significant effects on PC3 cell viability. However, the combination of SV and Li in all tested concentrations decreased the viability of PC3 cells in a dose dependent manner (P < 0.001). The combination of SV and Li (5.0 μM + 5.0 mM) increased apoptosis of PC3 cells compared with the control group (P = 0.003). Transwell assay showed that combination of SV with Li (5.0 μM + 5.0 mM) reduced the migration and invasion of PC3 cells significantly. The lack of a significant difference between the predicted and observed fractional inhibition for the effects of SV+Li suggests that SV and Li may have additive effects on lowering PC3 cell viability and invasiveness. These findings show that combined low doses of SV and Li could decrease the viability and invasiveness of the PC3 cells; therefore, it can be considered as a new strategy for the treatment of prostate cancer. However, further in vivo studies are required to confirm the results of this study.

Cervical cancer (CC) is the second most common type of cancer among women. A key factor in developing the disease is the human papillomavirus (HPV) infection. Aberrant DNA hypermethylation in gene promoter regions is one of the most well-fined epigenetic alterations in tumors. This study aimed to investigate cell adhesion molecule 1 (CADM1), promoter methylation in HPV serological positive samples in the Iranian population.
Genomic DNA was extracted from cervical smears from patients and healthy patients acting as a control group for this analytical observational case-control investigation. Reverse dot blotting was performed to first identify the presence of HPV DNA infection. After that, each sample was transformed by being treated with sodium bisulfite, and MSP was then used to determine the CADM1 gene's level of methylation.
Among total number of positive HPV samples (n = 52), 63.5% methylated, 23% hemi-methylated, and 13.5% were unmethylated. On the contrary, in the control group (n=38), 11% methylated, 71% hemi-methylated, and 18% were unmethylated (P < 0.0001). Furthermore, comparing the methylation status among high, low and high/low patients indicated that methylation was (66.66, 24.24, and 9.09%), (25, 66.66, and 8.33%), and (14.28, 57.14%, and 28.57%), respectively (P < 0.0001).
The present study confirmed that the methylation status of CADM1 gene was significantly higher in HPV-positive patients than in patients negative for HPV DNA. Moreover, the CADM1 pattern of the gene was associated with the highrisk subtypes of HPV, not with the low-risk ones. Therefore, CADM1 methylation appeared to be a promising biomarker for future studies.

Autologous stem cell transplant (ASCT) has been used as a consolidative treatment modality in non-Hodgkin’s lymphoma (NHL), but its role in NHL management is still evolving. The study aimed to evaluate the patient outcomes based on age, NHL subtypes, and conditioning regimen. We performed a retrospective analysis of NHL patients who received ASCT (n = 140) in our centre from 1992-2015. Data were gathered for this investigation using electronic records and case notes. Refractory illness, relapse, progressive disease, or death were all considered progression events. Time from ASCT to the last follow-up or progression event was used to define progression-free survival (PFS), and time from ASCT to death or the final follow-up was used to define overall survival (OS). Median age at ASCT was 55 years (16-68). Amongst patients ≤60 years (n = 109) and >60 years (n = 31), there was no significant difference in PFS (P = 0.756), OS (P = 0.711), neutrophil (12.5 vs. 11 days) and platelet (12 vs. 14 days) engraftment times. Amongst follicular lymphoma patients (n = 54) who received BEAM (carmustine, etoposide, cytarabine, melphalan) (n = 30) or Cy/TBI (cyclophosphamide/ total body irradiation) (n=24) conditioning, there was no significant difference between PFS (P = 0.111) and OS (P = 0.667). There was no significant difference (P = 0.46) in the incidence of second malignancies in the patient receiving BEAM or TBI-based conditioning. ASCT can be safely performed for NHL in patients >60 years with outcomes similar to those ≤60 years. TBI based conditioning appear safe with similar outcomes to BEAM in follicular lymphoma patients. Prospective studies are needed to confirm these findings.

Cognitive impairment is one of the common problems in patients undergoing radiotherapy, but there is no way to prevent it until this time. The aim of this study was to determine the effect of memantine on the prevention of cognitive impairment in patients with brain tumour undergoing radiotherapy. In this clinical trial study, 70 patients under radiotherapy were selected and randomly divided into two groups. The first group received 10 mg of memantine tablets daily for six months and the second group received placebo at the same dose and time. Cognitive impairment was evaluated through Mini-Mental Status Examination questionnaire and compared between the two groups. The mean score of cognitive impairment before and after radiotherapy in the control and intervention groups were 27.97 ± 1.52 and 27.66 ± 1.35 (P = 0.26), in the following month were 27.74 ± 1.74 and 27.63 ± 1.35 (P = 0.73), in the following three months were 23.17 ± 1.81 and 24.77 ± 1.44 (P < 0.001), and in the following six months were 20.66 ± 1.8 and 23.17 ± 1.42 (P < 0.001). In addition, changes in cognitive impairment score were significantly different between the two groups (P < 0.001). It seems that memantine is effective in preventing the cognitive impairment in patients undergoing radiotherapy following brain tumour surgery and the implementation of this referee can be associated with improved cognitive function over time.

Minimizing the overall treatment time is an issue of great importance in cancer management. Concomitant boost is a way of decreasing the overall treatment time in breast cancer. The present prospective randomized study aimed to evaluate the feasibility and toxicity and cosmetic outcome of concomitant weekly boost in patients with breast cancer.
Patients with breast cancer who underwent breast conservation surgery and were referred to our Radiation Oncology department from 2018 to 2019 were included in this randomized clinical trial. They were randomized to two groups both of which received conventional (50 Gy in 25 fraction, 5 days a week) whole breast irradiation (WBI) with 10 Gy boost dose to lumpectomy cavity. The boost dose in one group (n = 40) was delivered concomitantly on the 6th day of each week. The other group (n = 42) received the boost dose sequentially after completion of conventional WBI. Skin toxicity and cosmetic outcome was compared between the two groups according to CTCAE-4 skin complications and Harvard criteria.
We did not observe any significant differences between the sequential and concomitant groups in terms of acute skin reaction within and one month after completion of radiotherapy. After one year of follow-up, no significant differences were seen concerning the cosmetic outcome between the two groups. No local recurrence was observed after 22 months of follow-up.
Accelerated radiotherapy with weekly concomitant boost in breast cancer patients was found to be feasible with an acceptable toxicity profile and cosmetic outcome during one year of follow-up.

Based on the special pattern of recurrence in the excision cavity, secondary computed tomography (CT) can be introduced after hypofractionated whole breast radiotherapy with early breast cancer, aiming for accurate delineation of tumor bed boost and reduced toxicity. This study aimed to assess the volumetric changes in the lumpectomy cavity before and after hypofractionated whole breast radiation therapy (WBRT) and related clinical factors.
This prospective study was designed and CT simulation was done for 45 patients from September 2019 to April 2020, two radiotherapy treatment planning were generated for each patient before and after hypofractionated WBRT. The tumor bed is defined using surgical clips, seroma, and postoperative alterations. Based on the original CT and tumor bed boost CT, statistically significant decrease was examined. The relationship between various factors and the volume decrease in the excision cavity was examined.
The median value of reduction in the excision cavity was 15.4 cm3 with the statistical significance (P < 0.001). In multivariate linear regression, the significant variable, which predict the volume reduction, was the presence of seroma (B = 24.48, confidence interval, 13.09 to 35.87, P < 0.001).
our results suggested significant benefit from resimulation before boost planning especially for patients with clinical evident seroma.

Hand-foot syndrome (HFS) is a prevalent skin reaction to cytotoxic systemic therapy, mainly Capecitabine.
The present study aimed to determine etiologies of HFS in addition to its prevention in colorectal cancer patients with Capecitabine-containing chemotherapy regimen.
In this randomized double-blinded study, we recruited 66 eligible patients. The first 33 patients received 25 mg captopril twice daily, while the other 33 were given two placebo tablets.
All the patients were assessable for safety and efficacy. Captopril demonstrated a favorable safety profile. The participants in the two groups did not have any significant differences in terms of the median age and the level of hemoglobin (P = 0.45, P = 0.06, respectively). However, the CEA tumor marker was significantly higher in those with HFS (P < 0.05). The incidence of HFS in men and women were 8 (18.6%) and 3 (13%) cases, respectively, and the patients’ sex did not affect the incidence of this syndrome (P = 0.73).
Furthermore, according to the stage of colorectal cancer, the difference between the two groups was significant (P < 0.05). Meanwhile, there were no significant differences concerning the grade of colorectal cancer (P = 0.2).
The results herein revealed that administration of captopril in colorectal cancer patients with Capecitabine-containing chemotherapy regimen reduced the symptoms and incidence of HFS.
On the other hand, CEA tumor marker and the stage of colorectal cancer were in correlation with incidence of HFS.

Lynch syndrome (LS) predisposes individuals to early-onset colorectal and other Lynch-associated cancer. This disorder is an autosomal dominant genetic disturbance caused by germline mutations in one of the mismatch repair genes. Different clinical and molecular criteria are used to diagnose LS. Microsatellite instability testing and immunohistochemistry are two widely used methods for the molecular screening of LS-associated cancers. According to the immunohistochemistry and Microsatellite instability testing, we introduce three Persian families with Lynch-like syndrome (LLS) who met clinical Amsterdam-II criteria and their probands were mismatch repair deficient. In the case of immunohistochemistry-MLH1 absent, BRAF-V600E mutation was evaluated to rule out the sporadic colorectal cancer cases. No pathogenic germline variants were found by next generation sequencing method. Multiplex ligation-dependant probe amplification technique was done to find large in/dels within MLH1/MSH2 genes of the probands. A two-exon deletion within MLH1 gene was eventually identified in one of the patients. Finally, we have represented a molecular pipeline to diagnose LLS based on literature review and the introduced cases.

Palliative cancer patients suffer from a condition which needs to take many medications for supportive care and comorbid illnesses management. Therefore, they are at risk of drug-rated problems, such as futile medications. We aimed to discover the futile medication occurrence and identification as well as medication futility associated predictor factors.

In a prospective cross-sectional study, we included patients with advanced/incurable malignancies admitted to Ala palliative clinic, a charity clinic affiliated to Omid Hospital in Isfahan, Iran, between June 2018 and April 2019. To identify the use of fruitless medicine towards the end of life, we conducted a thorough analysis of the demographic information and prescription lists of terminally ill patients. The phrase "futile drugs" refers to those that are superfluous or redundant, have no significant benefits in terms of illness symptom management or survival time extension, or have a long-term chronic usage.

From 133 involved patients, 114 (85.7%) were considered to use at least one futile medication (including only administration of unnecessary medications (70%) or both unnecessary and duplicate medication (30%). 35 patients were encountered with 48 medication duplications of the different pharmacological class of medications mostly opioids (33%). According to multivariate logistic regression analysis, the number of drugs and the average time to death were related with the prevalence of medication futility.

Palliative cancer patients were exposed to taking futile medications. More different prospective studies are warranted to evaluate the clinical and economic impact of futile medication use in oncology practice.

Medullary thyroid carcinoma (MTC) is the third most prevalent thyroid cancer and the most invasive form. This malignancy could be presented either in a sporadically or a familial pattern. Although the majority of cases with this disease are presented sporadically, familial screening is of great necessity in every MTC case since of all heritable cancers, MTCs are the most common malignancies. Therefore, after the familial screening of MTC patients using clinical symptoms along with paraclinical tools, the present study identified 19 familial medullary thyroid carcinoma (FMTC) cases in one family. Since most FMTCs are associated with multiple endocrine neoplasia’s (MEN's) syndrome, it has attracted a great deal of scientific attention. This syndrome was ruled out herein through both genetic and clinical testing in these individuals. Thus, due to the scarcity of the familial form of this disease, the significant number of MTC in a family, and the absence of MEN syndrome in these people, we decided to report 19 patients with MTC in the same family without MEN’s syndrome from southwest of Iran; this report emphasizes the necessity of familial screening even in the absence of the MEN's syndrome.

Clear cell carcinoma is believed to be one of the rare neoplasms of cervix uteri and vagina. The etiology and pathogenesis of clear cell carcinoma of the cervix are unclear, with scarce information about the clinical behavior, optimal management, and prognosis of the tumor. The current treatment options are based on the experiences accumulated on squamous cell carcinoma and other types of adenocarcinoma. Prior intrauterine exposure to diethylstilbestrol (DES) is presumed to be a predisposing factor for clear cell adenocarcinoma in young patients. Metastasis is uncommon, but local recurrence may occur. The cure rate of this disease is 85%-90% in early stages with a small volume of tumors. In this study, we report a rare case of clear cell carcinoma of the cervix in a 21-year-old woman, who had no exposure to DES (in-utero) or synthetic non-steroidal estrogen; therefore, the present research supports the hypothesis that the risk factors, other than DES exposure, play an important role in carcinogenesis.

Colon cancer is one of the commonest tumours in the world. Although most colon cancer patients are colonized by adenocarcinoma, some other pathologies such as adenosquamous carcinoma are rarely encountered. We present two patients with right colon adenosquamous carcinoma. Both patients were males and both suffered a nodepositive disease. Furthermore, one of them developed recurrence 7 months after initial radical surgery, despite formal colon adjuvant chemotherapy given. In conclusion, the patients with adenosquamous colon cancer are a subgroup with a worse prognosis, and questionable response to the conventional chemotherapeutic regimens as FOLFOX (flourouracil, leucoverin, and oxaloplatin) and CAPEOX (capecitabine and oxaloplatin).

The most common cancer in women is breast cancer (BC) with an incidence of 24.2%. BC in younger patients will in general be more forceful, prompting more awful results and a requirement for more forceful treatment which may bring about a higher probability of long-haul treatment-related harmfulness and novel psychosocial issues. Furthermore, family inclination to BC as BRCA1 and BRCA2 mutations is more prevalent in this age group. There were a total of five ladies who had tumor pathology testing with negative results. All intrusive BC examples were regularly assessed for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2)/neu status utilizing immunohistochemistry. Cases with HER2/neu staining of 1+, 2+ or 3+ on immunohistochemistry examination were additionally assessed by fluorescent in situ hybridization for the enhancement of the HER2/neu quality. In this examination, we distinguished clinicopathological attributes of patients with BC. We partitioned into two gatherings, BRCA positive change and BRCA negative transformation. Roughly 5%-10% instances of BC have a positive family ancestry and about 20%-40% BC development were in acquired variations. Our study revealed that 20% of cases included individuals who had a family history of BRCA mutation. Male relatives with BC, earlier age at onset, a greater prevalence of reciprocal breast disease, and a connection to various malignancies in the ovary, colon, prostate, pancreas, and endometrial are only a few of the clear clinical characteristics of BRCA1/2-related BC.

Sebaceous carcinoma is a rare and invasive tumor that originates from the Zeis and Meibomian glands around the eyes as well as in sebaceous glands in other head and neck areas and less commonly on the trunk. We report an 82-year-old Iranian man with a sebaceous carcinoma on the left external ear that was successfully treated with radiotherapy.

Brain glioblastoma multiforme with leptomeningeal metastasis is a rare medical condition. Although autopsy series have demonstrated a higher incidence of leptomeningeal metastasis, it is usually a late complication in the course of the disease. The disease progression is almost always rapid, resulting in a poor performance status and short survival. There is no single standard treatment but different individualized choices including chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation have been utilized. In this manuscript, we report a male patient with glioblastoma multiforme of left prefrontal lobe that presented with concomitant cervical leptomeningeal metastasis. Because of poor performance, he received hypofractionated radiotherapy of brain and cervical spine which consisted of a total dose of 45 Gy in 10 fractions with 300c Gy per fraction and 30 Gy local boost to the areas of enhancement. Despite this treatment, there was no response and the patient died three days after the completion of the treatment.