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Saudi Arabia

Cancer Statistics
Population in 2008: 25.2m
People newly diagnosed with cancer (excluding NMSC) / yr: 13,300
Age-standardised rate, incidence per 100,000 people/yr: 87.6
Risk of getting cancer before age 75:8.9%
People dying from cancer /yr: 8,900
Data from IARC GlobalCan (2008)
Saudi Arabia Cancer Organisations and Resources
Latest Research Publications Related to Saudi Arabia

Saudi Arabia Cancer Organisations and Resources (10 links)


Latest Research Publications Related to Saudi Arabia

Chrisinger JSA, Al-Zaid T, Keung EZ, et al.
The degree of sclerosis is associated with prognosis in well-differentiated liposarcoma of the retroperitoneum.
J Surg Oncol. 2019; 120(3):382-388 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Well-differentiated liposarcomas (WDL) are often partly composed of sclerotic tissue, however, the amount varies widely between tumors, and its prognostic significance is unknown. We hypothesized that tumors with more sclerosis would behave more aggressively.
METHODS: Primary retroperitoneal WDL from 29 patients resected at our institution with follow-up were histologically evaluated by soft tissue pathologists blinded to outcome. Tumors with ≥ 10% sclerosis were designated "sclerotic" while tumors with < 10% sclerosis were designated as "minimally sclerotic". Cellular and dedifferentiated tumors were excluded. Clinical parameters and radiologic assessments on computed tomography (CT) were recorded.
RESULTS: Histological evaluation identified 13 minimally sclerotic WDL and 16 sclerotic WDL. Median follow-up was 9 years (range, 3-20). Median recurrence-free survival (RFS) and median overall survival (OS) were 6.16 and 13.9 years, respectively. Compared with patients with sclerotic WDL, those with minimally sclerotic WDL had superior RFS (HR = 0.17 [95% CI, 0.06-0.53], P = .002) and OS (log-rank test, P = .002). Sclerotic WDL exhibited higher Houndsfield Units than minimally sclerotic WDL (26 vs 1, P = .040).
CONCLUSIONS: Minimally sclerotic WDL were associated with more favorable outcome compared with sclerotic tumors. Assessment of sclerosis in WDL is likely a useful prognostic marker.

Masoodi TA, Shaik NA, Burhan S, et al.
Structural prediction, whole exome sequencing and molecular dynamics simulation confirms p.G118D somatic mutation of PIK3CA as functionally important in breast cancer patients.
Comput Biol Chem. 2019; 80:472-479 [PubMed] Related Publications
To understand the structural and functional importance of PIK3CA somatic mutations, whole exome sequencing, molecular dynamics simulation techniques in combination with in silico prediction algorithms such as SIFT, PolyPhen, Provean and CADD were employed. Twenty out of eighty missense somatic mutations in PIK3CA gene were found to be pathogenic by all the four algorithms. Most recurrent mutations found were known hotspot PIK3CA mutations with known clinical significance like p.E545 K, p.E545A, p.E545 G and p.C420R. A missense mutation p.G118D was found to be recurrently mutated in 5 cases. Interestingly, this mutation was observed in one of the patients who underwent whole exome sequencing and was completely absent from the controls. To see the effect of this mutation on the structure of PIK3CA protein, molecular dynamics simulation was performed. By molecular dynamics approach, we have shown that p.G118D mutation deviated from the native structure which was supported by the decrease in the number of hydrogen bonds, difference in hydrogen bond distance and angle, difference in root mean square deviation between the native and the mutant structures.

Salem S, Saad I, Alamri R
Thymoma associated myasthenia gravis with atypical presentation of lipomatous tongue atrophy: a case report.
Pan Afr Med J. 2019; 32:38 [PubMed] Free Access to Full Article Related Publications
A 28-year-old female patient came to the outpatient dental clinic for multiple teeth extractions and full mouth rehabilitation suffer from myasthenia gravis (MG) primary presentation as tongue atrophy and facial muscles weakness and the symptoms became worries, the patient unable to speak as well and change her voice and complaining of dysphagia and dysarthria. Oral symptoms, treatment schedule and protocol, the selection, prescription and impacts of medications, and prevention of myasthenic crisis are all important; aspects should be considered by dentists and oral health care providers. Weakness of facial and oropharyngeal muscle is considered very popular at disease onset and therefore oral health providers are often the first medical professionals to observe these patients. Myasthenic patients seek particular approach and consultation in order to ensure ideal and proper dental management.

Gunness VRN, Munoz D, González-López P, et al.
Ipsilateral brain cavernoma under scleroderma plaque: a case report.
Pan Afr Med J. 2019; 32:13 [PubMed] Free Access to Full Article Related Publications
Scleroderma is a rare disease of unknown etiology, which is characterized by thickening and hardening of skin due to an increased collagen production. A 44-year-old female patient with a scleroderma on the scalp known by our department, also presented an ipsilateral brain lesion since 2015, which was showing growth without any clinical symptomatology and the patient wanted the lesion to be removed. This atypical lesion underneath the scleroderma shows that diagnosis can be missed without brain imaging and biopsy.

Law PJ, Timofeeva M, Fernandez-Rozadilla C, et al.
Association analyses identify 31 new risk loci for colorectal cancer susceptibility.
Nat Commun. 2019; 10(1):2154 [PubMed] Free Access to Full Article Related Publications
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

Albasri AM, Ansari IA, Aljohani AR, Alhujaily AS
Granular cell tumour of the breast in a young female: A case report and literature review.
Niger J Clin Pract. 2019; 22(5):742-744 [PubMed] Related Publications
A granular cell tumour (GCT) of the breast is a relatively uncommon lesion. Often, it mimics carcinoma on clinical and radiological examinations. The striking feature of GCT is the presence of abundant granular eosinophilic cytoplasm, which can easily lead to a misdiagnosis of apocrine carcinoma or a metastatic lesion and may result in unnecessary surgery. To obtain a correct diagnosis, immunohistochemistry with S100 is required. We present a case of a GCT of the breast in a 19-year-old female who presented with a firm mass in the upper inner quadrant of the left breast, which was reported on a mammogram as the Breast Imaging Reporting and Data System (BIRADS) Category 4C. This report is of interest due to the young age of the patient and the rarity of the lesion. To our knowledge, this is the second reported case in all of Saudi Arabia and the first from the Madinah region.

Proietti S, Cucina A, Pensotti A, et al.
Active Fraction from Embryo Fish Extracts Induces Reversion of the Malignant Invasive Phenotype in Breast Cancer through Down-regulation of TCTP and Modulation of E-cadherin/β-catenin Pathway.
Int J Mol Sci. 2019; 20(9) [PubMed] Free Access to Full Article Related Publications
Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embryos during specific developmental phases (20 somites) significantly antagonize proliferation of breast cancer cells, while reversing a number of prominent aspects of malignancy. Embryo extracts reduce cell proliferation, enhance apoptosis, and dramatically inhibit both invasiveness and migrating capabilities of cancer cells. Counteracting the invasive phenotype is a relevant issue in controlling tumor spreading and metastasis. Moreover, such effect is not limited to cancerous cells as embryo extracts were also effective in inhibiting migration and invasiveness displayed by normal breast cells undergoing epithelial-mesenchymal transition upon TGF-β1 stimulation. The reversion program involves the modulation of E-cadherin/β-catenin pathway, cytoskeleton remodeling with dramatic reduction in vinculin, as well as downregulation of TCTP and the concomitant increase in p53 levels. Our findings highlight that-contrary to the prevailing current "dogma", which posits that neoplastic cells are irreversibly "committed"-the malignant phenotype can ultimately be "reversed", at least partially, in response to environmental morphogenetic influences.

Ahmad ST, Rogers AD, Chen MJ, et al.
Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors.
Nat Commun. 2019; 10(1):2000 [PubMed] Free Access to Full Article Related Publications
Capicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic's function in the brain. We show that nuclear Cic expression is strongest in astrocytes and neurons but weaker in stem cells and oligodendroglial lineage cells. Using a new conditional Cic knockout mouse, we demonstrate that forebrain-specific Cic deletion increases proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage effects are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal, and tumorigenicity. Our results identify Cic as an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.

Thaventhiran T, Wong W, Alghanem AF, et al.
CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program.
Monoclon Antib Immunodiagn Immunother. 2019; 38(2):60-69 [PubMed] Free Access to Full Article Related Publications
CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4

Khan FA, Akhtar S, Almohazey D, et al.
Targeted delivery of poly (methyl methacrylate) particles in colon cancer cells selectively attenuates cancer cell proliferation.
Artif Cells Nanomed Biotechnol. 2019; 47(1):1533-1542 [PubMed] Related Publications
Poly (methyl methacrylate) (PMMA) is basically biocompatible polyester with high resistance to chemical hydrolysis, and high drug permeability and the most important characteristics of PMMA is that it does not produce any toxicity. There is not much information about PMMA action on the colon cancer cells. In the present study, we have synthesized PMMA nanoparticles. The distribution pattern of PMMA particles was analysed by Zeta sizer and the size of the particles was calculated by using quasi elastic light scattering (QELS). The surface structure and the morphology of PMMA were characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM), respectively. We have also analysed their effects on cancerous cells (human colorectal carcinoma cells, HCT-116) and normal, healthy cells (human embryonic kidney cells, HEK-293) by using morphometric, MTT, DAPI and wound healing methods. We report that PMMA particles inhibited the cancer cell viability in a dose-dependent manner. The lower dose (1.0 μg/ml) showed a moderate decrease in cancer cell viability, whereas higher dosages (2.5 μg/ml, 5.0 μg/mL and 7.5 μg/mL) showed steadily decrease in the cancer cell viability. We also report that PMMA is highly selective to cancerous cells (HCT-116), as we did not find any action on the normal healthy cells (HEK-293). In conclusion, our results suggest PMMA particles are potential biomaterials to be used in the treatment of colon cancer.

Al-Ghabkari A, Qasrawi DO, Alshehri M, Narendran A
Focal adhesion kinase (FAK) phosphorylation is a key regulator of embryonal rhabdomyosarcoma (ERMS) cell viability and migration.
J Cancer Res Clin Oncol. 2019; 145(6):1461-1469 [PubMed] Related Publications
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Pathogenesis of RMS is associated with aggressive growth pattern and increased risk of morbidity and mortality. There are two main subtypes or RMS: embryonal and alveolar. The embryonal type is characterized by distinct molecular aberrations, including alterations in the activity of certain protein kinases. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a vital role in focal adhesion (FA) assembly to promote cytoskeleton dynamics and regulation of cell motility. It is regulated by multiple phosphorylation sites: tyrosine 397, Tyr 576/577, and Tyr 925. Tyrosine 397 is the autophosphorylation site that regulates FAK localization at the cell periphery to facilitate the assembly and formation of the FA complex. The kinase activity of FAK is mediated by the phosphorylation of Tyr 576/577 within the kinase domain activation loop. Aberrations of FAK phosphorylation have been linked to the pathogenesis of different types of cancers. In this regard, pY397 upregulation is linked to increase ERMS cell motility, invasion, and tumorigenesis.
METHODS: In this study, we have used an established human embryonal muscle rhabdomyosarcoma cell line RD as a model to examine FAK phosphorylation profiles to characterize its role in the pathogenies of RMS.
RESULTS: Our findings revealed a significant increase of FAK phosphorylation at pY397 in RD cells compared to control cells (hTERT). On the other hand, Tyr 576/577 phosphorylation levels in RD cells displayed a pronounced reduction. Our data showed that Y925 residue exhibited no detectable change. The in vitro analysis showed that the FAK inhibitor, PF-562271 led to G1 cell-cycle arrest induced cell death (IC
CONCLUSIONS: The data presented herein indicate that targeting FAK phosphorylation at distinct sites is a promising strategy in future treatment approaches for defined subgroups of rhabdomyosarcoma.

Alkuwaiti FA, Elghoneimy Y, Ghazal S
Aortic Valve
Sultan Qaboos Univ Med J. 2018; 18(4):e537-e540 [PubMed] Free Access to Full Article Related Publications

Felemban AA, Rashidi ZA, Almatrafi MH, Alsahabi JA
Autoimmune hemolytic anemia and ovarian dermoid cysts in pregnancy.
Saudi Med J. 2019; 40(4):397-400 [PubMed] Free Access to Full Article Related Publications
Ovarian teratoma is a rare cause of autoimmune hemolytic anemia (AIHA) by warm antibodies, resistant to corticosteroid therapy. This also implies that ovarian teratoma should be included in the differential diagnosis of AIHA, whether or not associated with pregnancy. We present a case of a primigravida who presented with ovarian dermoid cysts and AIHA at 24 weeks of gestation. The patient received corticosteroids, intravenous immunoglobulin, rituximab, and multiple blood transfusions, with no significant improvement. Hemoglobin levels returned to normal only after laparoscopic ovarian cystectomy. Autoimmune hemolytic anemia caused by dermoid cyst is a rare condition especially in pregnancy. However, in light of similar case reports and review of the existing literature, we conclude that surgical excision should be considered when AIHA and ovarian teratoma coexist.

Alsagaby SA
Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness.
Saudi Med J. 2019; 40(4):328-338 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To use independent transcriptomics data sets of cancer patients with prognostic information from public repositories to validate the relevance of our previously described chronic lymphocytic leukemia (CLL)-related proteins at the level of transcription (mRNA) to the prognosis of CLL.  Methods: This is a validation study that was conducted at Majmaah University, Kingdom of Saudi Arabia between January-2017 and July-2018. Two independent data sets of CLL transcriptomics from Gene Expression Omnibus (GEO) with time-to-first treatment (TTFT) data (GSE39671; 130 patients) and information about overall survival (OS) (GSE22762; 107 patients) were used for the validation analyses. To further investigate the relatedness of a transcript of interest to other neoplasms, 6 independent data sets of cancer transcriptomics with prognostic information (1865 patients) from the cancer genomics atlas (TCGA) were used. Pathway-enrichment analyses were conducted using Reactome; and correlation analyses of gene expression were performed using Pearson score. Results: Nine of the CLL-related proteins exhibited transcript expression that predicted TTFT and 7 of the CLL-related proteins showed mRNA levels that predicted OS in CLL patients (p≤0.05). Of these transcripts, 8 were different types of heterogeneous nuclear ribonucleoproteins (HNRNPs); and 2 (HNRNPUL2 and HIST1C1H) retained prognostic significance in the 2 independent data sets. Furthermore, genes that enriched CLL-related pathways (p≤0.05; false discovery rate [FDR] ≤0.05) were found to correlate with the expression of HNRNPUL2 (Pearson score: ≥0.50; p lessthan 0.00001). Finally, increased expression of HNRNPUL2 was indicative of poor prognosis of various types of cancer other than CLL (p less than 0.05). Conclusion: The cognate transcripts of 14 of our CLL-related proteins significantly predicted CLL prognosis.

Alsagaby SA, Alhumaydhi FA
Proteomics insights into the pathology and prognosis of chronic lymphocytic leukemia.
Saudi Med J. 2019; 40(4):317-327 [PubMed] Free Access to Full Article Related Publications
Chronic lymphocytic leukemia (CLL) is an incurable malignant disease of B-lymphocytes characterized by drastically heterogeneous clinical courses. Proteomics is an advanced approach that allows a global profiling of protein expression, providing a valuable chance for the discovery of disease-related proteins. In the last 2 decades, several proteomics studies were conducted on CLL to identify aberrant protein expression underpinning the malignant transformation and progression of the disease. Overall, these studies provided insights into the pathology and prognosis of CLL and reveal protein candidates with the potential to serve as biomarkers and/or therapeutic targets of the tumor. The major findings reported in these studies are discussed here.

Algahtani H, Shirah B, Seddeq Y, Al-Maghraby H
Hemorrhagic Brain Metastasis as the Initial Manifestation of Esophageal Adenocarcinoma.
Gulf J Oncolog. 2019; 1(29):87-90 [PubMed] Related Publications
Esophageal carcinoma metastasis to the brain is very rare with less than 300 cases published worldwide. The reported incidence rates of esophageal carcinoma metastases to the brain range from 0.3% to 13%. It is associated with a worse prognosis than brain metastases from other solid tumors. The most common form of metastasis is cystic lesions while hemorrhagic metastasis represents a rare subset of an infrequent entity. It is extremely rare for esophageal carcinoma to present as an isolated brain metastasis with only three cases reported worldwide. These cases were misdiagnosed as meningitis, a pituitary tumor, and glioma. This paper reports the first case of hemorrhagic brain metastasis as the initial and only manifestation of esophageal adenocarcinoma worldwide. Although extensive work up to search for malignancy is a routine procedure in patients with metastatic brain disease, upper gastrointestinal endoscopy, which is rarely done as part of the work up should be included. Esophageal cancer continues to be challenging to manage with very limited therapeutic options. To date, the clinical outcome after treatment is unsatisfactory, and prognosis is poor. Further research is required to identify better treatment approaches and improve the survival of patients. This paper is an urgent call for action to design chemotherapeutic agents that target tumor cells in the blood and different body organs and has the ability to cross the blood-brain barrier with an acceptable side effect profile. This is mainly because metastatic brain disease has become more common in young age group.

Alobaid A, Elamir H, Abuzaid M, Abu-Zaid A
An Extremely Giant Ovarian Mucinous Cystadenoma.
Gulf J Oncolog. 2019; 1(29):83-86 [PubMed] Related Publications
Ovarian mucinous cystadenomas are cystic neoplasms lined by mucin-producing epithelial cells. They are mostly benign (80%) and frequently asymptomatic at early stages. The average diameter of ovarian mucinous cystadenomas ranges from 15 to 30 cm. Herein, we report the case of a giant benign ovarian mucinous cystadenoma in a 53-year-old postmenopausal woman. The patient presented with a very huge pelvi-abdominal distention that started ten months ago and was progressively increasing in size. It was associated with on-off abdominal pain, nausea and urinary retention. The case was discussed with a multidisciplinary team. Subsequently, the patient was consented for exploratory laparotomy. The origin of the mass was identified to be the right ovary, and right salpingo-oophorectomy was done. The resected mass measured 73x51x42 cm and weighed 108 kg. The left ovary had a multilocular mass of 15 cm in diameter, and left salpingo-oophorectomy was successively performed. There was no ascites. Histopathological examination confirmed the diagnosis of bilateral benign mucinous cystadenoma. At a postoperative 9-month follow-up in the outpatient clinic, the patient showed up in good condition without evidence of recurrence. To the best of our knowledge, we report the largest benign ovarian cyst in Saudi Arabia, and one of the largest (probably the third) in the English medical literature. It is technically feasible to manage an extremely large-sized benign mass with satisfactorily perioperative outcomes. This should be done through a multidisciplinary approach that demands an orchestrated collaboration between different specialists to yield an optimized perioperative care.

Alattas MT
Cancer Control Priorities and Challenges in Saudi Arabia: A Preliminary projection of Cancer Burden.
Gulf J Oncolog. 2019; 1(29):22-30 [PubMed] Related Publications
INTRODUCTION: Saudi Arabia faces a rapid growth in cancer cases and deaths despite the rapid development and expansion of its healthcare system. No applied national strategies exist, limiting cancer control efforts. Saudi Cancer Registry data lacks cancer specific mortality rates and available data to project the future cancer burden is inadequate.
METHODS: This review paper examines the extent which cancer burden will increase by providing an estimate projection of cancer cases and deaths for the year 2025 and 2050. Current cancer burden and gaps are discussed. Saudi population projections were used to predict the burden of cancer types with the highest mortality. Rough estimates of the burden were calculated using incidence and mortality rates adopted from available UK cancer data and population figures from Office for National Statistics.
FINDINGS: For most common cancers in Saudi Arabia, it is expected that the number of new cancer cases will reach 151,719 by the year 2025 and 30,718 cancer deaths are expected for the same year. Evidence from other countries' efforts to control cancer demonstrates reduced mortality and points out the substantial need to urgently update cancer control strategy.
DISCUSSION AND CONCLUSION: Reviewing current trends in cancer burden in Saudi Arabia and projecting the future burden, especially of breast and colon cancers, proves the need to prioritize cancer control efforts. Planning a multidisciplinary evidence based national cancer control strategy will alleviate the burden and improve cancer outcomes.

Li AJ, Feldman SM, McNally RK, Kannan K
Distribution of Organohalogen and Synthetic Musk Compounds in Breast Adipose Tissue of Breast Cancer Patients in Ulster County, New York, USA.
Arch Environ Contam Toxicol. 2019; 77(1):68-78 [PubMed] Related Publications
We determined the concentrations of 98 halogenated organic compounds and synthetic musks in breast fat tissues of 50 breast cancer patients (age range: 34-77 years) collected during 1996-1998 in Ulster County, New York, USA. Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated biphenyl 153 (PBB-153), polybrominated diphenyl ethers (PBDEs), and synthetic musk compounds (SMCs) were analyzed in breast fat tissues, and 46 analytes were found at a detection frequency of ≥ 65% and at concentrations in the decreasing order of OCPs > PCBs > SMCs > PBDEs > PBB-153. PCBs (median: 323 ng/g wet wt) and dichlorodiphenyltrichloroethanes (DDTs, median: 293 ng/g wet wt) were the major compounds found in breast fat tissues. Among PCB congeners, hexa- and hepta-chlorobiphenyls (60% of total PCBs) were the abundant ones. p,p'-DDE accounted for more than 99% of the total DDT concentrations. The concentrations of SMCs and PBDEs were 1-2 orders of magnitude lower than those of PCBs and DDTs. 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-r-2-benzopyran (median: 33 ng/g wet wt) was the most abundant SMC, whereas BDE-47 (median: 4.5 ng/g wet wt) was the most dominant PBDE congener present in breast tissues. A significant correlation (p < 0.05) between women's age and concentrations of DDTs, chlordanes, hexachlorobenzene and PCBs in breast tissues was found. Concentrations of PCBs, PBDEs, OCPs, and SMCs were not significantly different between malignant and benign tumor cases. This study adds baseline information on target tissue burdens of persistent organic contaminants in breast cancer patients.

Atef A, El-Rashidy MA, Elzayat S, Kabel AM
The prognostic value of sex hormone receptors expression in laryngeal carcinoma.
Tissue Cell. 2019; 57:84-89 [PubMed] Related Publications
Laryngeal cancer was identified as the second most common respiratory system malignancy with squamous cell carcinoma being the most common malignant tumor of the larynx. Larynx being a secondary sex organ showing physiological changes during puberty, raises inquiry about the relationship between sex hormones receptors as estrogen receptors (ER), progesterone receptors (PR), androgen receptors (AR) and the development of laryngeal carcinoma. This study was carried out in cancer tissue samples from 50 patients with laryngeal squamous cell carcinoma. Immunohistochemical staining using ER-β, PR, and AR was carried out. The immunohistochemical expression of ER-β, PR and AR was positive in 56%, 50% and 64% of cases respectively. ER-β, and PR expression were significantly higher in poorly differentiated cases and cases with lymphatic invasion while AR expression was significantly lower in poorly differentiated cases and with lymphatic invasion. In conclusion, ER-β and PR may be considered as markers for poor biological behavior of laryngeal carcinoma.

Ibrahim SM, Bakhashab S, Ilyas AM, et al.
WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines.
Oncol Rep. 2019; 41(6):3179-3188 [PubMed] Free Access to Full Article Related Publications
Multidrug resistance (MDR) is a major reason for the failure of acute myeloid leukemia (AML) therapy. Agents that reverse MDR and sensitize AML cells to chemotherapy are of great clinical significance. The present study developed Adriamycin (Adr)‑resistant cell lines, namely K562/Adr200 and K562/Adr500, which exhibited MDR. The upregulation of ATP‑binding cassette subfamily B member 1 (ABCB1) was confirmed as the mechanism of resistance by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Subsequently, the role of the mammalian target of rapamycin (mTOR) kinase inhibitor, WYE‑354, in sensitizing the K562/Adr200 and K562/Adr500 cell lines to Adr was evaluated. At sub‑cytotoxic concentrations, WYE‑354 increased Adr cytotoxicity in the K562/Adr200 and K562/Adr500 cells. WYE‑354 restored Adr sensitivity in the resistant cells by inhibiting ABCB1‑mediated substrate efflux, thereby leading to an accumulation of Adr, an increase in Adr‑mediated G2/M cell cycle arrest and the induction of apoptosis. Furthermore, WYE‑354 stimulated the ATPase activity of ABCB1, which was consistent with in silico predictions using a human ABCB1 mouse homology model, indicating that WYE‑354 is a potent substrate of ABCB1. WYE‑354 did not regulate the expression of ABCB1 at the concentrations used in the present study. These findings indicate that WYE‑354 may be a competitive inhibitor of ABCB1‑mediated efflux and a potential candidate in combination with standard chemotherapy for overcoming MDR. Further clinical investigations are warranted to validate this combination in vivo.

Alharthi T, Arumugam S, Vial P, et al.
EPID sensitivity to delivery errors for pre-treatment verification of lung SBRT VMAT plans.
Phys Med. 2019; 59:37-46 [PubMed] Related Publications
PURPOSE: To study the sensitivity of an Electronic Portal Imaging Device (EPID) in detecting delivery errors for VMAT lung stereotactic body radiotherapy (SBRT) using the Collapsed Arc method.
METHODS: Baseline VMAT plans and plans with errors intentionally introduced were generated for 15 lung SBRT patients. Three types of errors were introduced by modifying collimator angles and multi-leaf collimator (MLC) field sizes (MLCFS) and MLC shifts by ±5, ±2, and ±1° or millimeters. A total of 103 plans were measured with EPID on an Elekta Synergy Linear Accelerator (Agility MLC) and compared to both the original treatment planning system (TPS) Collapsed Arc dose matrix and the no-error plan baseline EPID measurements. Gamma analysis was performed using the OmniPro-I'mRT (IBA Dosimetry) software and gamma criteria of 1%/1 mm, 2%/1 mm, 2%/2 mm, and 3%/3.
RESULTS: When the error-introduced EPID measured dose matrices were compared to the TPS matrices, the majority of simulated errors were detected with gamma tolerance of 2%/1 mm and 1%/1 mm. When the error-introduced EPID measured dose matrices were compared to the baseline EPID measurements, all the MLCFS and MLC shift errors, and ±5°collimator errors were detected using 2%/1 mm and 1%/1 mm gamma criteria.
CONCLUSION: This work demonstrates the feasibility and effectiveness of the collapsed arc technique and EPID for pre-treatment verification of lung SBRT VMAT plans. The EPID was able to detect the majority of MLC and the larger collimator errors with sensitivity to errors depending on the gamma tolerances.

Ahmed A
Chondroid and osseous metaplasia in an incidental type II papillary renal cell carcinoma with extensive solid areas: an unraveled molecular character.
Pan Afr Med J. 2018; 31:26 [PubMed] Free Access to Full Article Related Publications
Chondroid and osseous metaplasia in a Type II Papillary renal cell carcinoma (PRCC) with extensive solid areas is a complex histological combination that has not been reported before. A 21 years old male presented with a comminuted fracture of right femur. On hematological investigations he was found to have low RBC count and hemoglobin. Radiological examination revealed an incidental, exophytic complex solid and cystic, mass lesion measuring 7 x 6.5 x 4.9 cm with thickened walls, septation and calcification. It was completely replacing upper pole of the left kidney with extension into perinephric fat. Enlarged para aortic and hilar nodes with necrosis were also noted. Radiological diagnosis was infectious processes such as tuberculosis versus malignancy. Surgical intervention comprising left partial nephrectomy was done. Histopathology and immunohistochemical analysis yielded the above diagnosis. Cytogenetic studies did not reveal gain of chromosome 7 and/or 17 or loss of chromosome Y, a characteristic genetic profile of PRCC. This case could be representative of a unique histological variant of PRCC in which the molecular profile yet needs to be unraveled.

Ahmed A
Prevalence of Her3 in gastric cancer and its association with molecular prognostic markers: a Saudi cohort based study.
Libyan J Med. 2019; 14(1):1574532 [PubMed] Free Access to Full Article Related Publications
Her 3 is a member of epidermal growth factor receptors. Mutated, oncogenic Her3 is reported in gastric and colonic cancers with emerging evidence that Her3 can be a potential target for molecular therapies. There is a paucity of studies regarding Her3 and its prognostic implications in gastric cancer in our region. In this study, we evaluated prevalence of Her3 in gastric cancer, in a Saudi cohort of cases, along with its association with prognostic markers p53 and Ki-67. The study was conducted in Department of Pathology of King Fahd Hospital of Imam Abdulrahman Bin Faisal University, Dammam, KSA. Fifty cases of gastric carcinoma were selected from the pathology files that fulfilled the inclusion criteria. Clinico-pathological parameters, Laurens histological classification, and immunohistochemical staining for Her3, p53, and Ki-67 were done. Her 3 positive cases were also evaluated for Her-2neu co-expression. Her3 positivity was seen in 16% (n = 8) out of a total of 50 cases. The median age of presentation was 44 years. Within Her3 positive cases, a female preponderance of 63% (n = 5), presence of high grade tumors in 75% (n = 6), diffuse gastric carcinoma in 63% (n = 5), diffuse to focal p53 positivity in 63% (n = 5), and a high to moderate Ki-67 proliferation index in 75% (n = 6) of cases was seen. Her3 expression was independent of Her-2neu status. Her3 prevalence of 16% with a median age of 44 years at presentation was less than in other reported studies, highlighting the concept of ethnic and regional variation in tumor characteristics. Her3 association with diffuse gastric carcinoma, high grade tumors, diffuse to focal p53 positivity and high to moderate Ki-67 proliferation index points towards a more aggressive clinical behavior.

Hassan FM
OGG1 rs1052133 Polymorphism and Genetic Susceptibility to Chronic Myelogenous Leukaemia
Asian Pac J Cancer Prev. 2019; 20(3):925-928 [PubMed] Related Publications
Background: In some cancer cells, the OGG1 gene is somatically mutated and highly populated. This study was conducted to examine whether OGG1 rs1052133 polymorphism is associated with the genetic background of chronic myelogenous leukaemia (CML) in Sudan. Methods: A total of 332 CML patients and 70 healthy controls were included in this study. Overall, the genotypes (P=0.0000) and allele (C vs. G, P=0.0007) differed considerably in the frequencies of OGG1 rs1052133 polymorphism between CML patients and controls. Our study is the first to evaluate the association of polymorphism with CML risk with OGG1 rs1052133. Results: A statistically significant association was observed between the genotype distribution of OGG1 rs1052133 polymorphism and CML (P=0.0000) patients. A similar result was also observed in the allele distribution (C vs. G, P=0.0007) compared with healthy controls when compared OGG1 rs1052133 genotypes with CML stages. Results: Genotype and allele frequencies of OGG1 rs1052133 among CML patients. A statistically significant association was observed between the genotype distribution of the OGG1 rs1052133 polymorphism and CML patients (P=0.0000). A similar result was also observed in the allele distribution (C vs. G, P=0.0007) compared with healthy controls with stages of CML in OGG1 rs1052133 genotypes. Conclusion: The results suggest that single nucleotide polymorphism in the gene involved in the restoration of DNA base excision (OGG1 rs1052133) can play a key role in the risk of appearance of CML. To clarify the role of OGG1 in the genetic basis of CML, further case control with larger sample sizes and fine-mapping is required.

Barakzai MA
Prostatic Adenocarcinoma: A Grading from Gleason to the New Grade-Group System: A Historical and Critical Review
Asian Pac J Cancer Prev. 2019; 20(3):661-666 [PubMed] Related Publications
The introduction of the Gleason grading system revolutionised prognostic parameters and determination of patient treatment regiments for prostatic adenocarcinomas, and has become synonymous with prostate cancer, almost universally applied in clinical settings to predict radical prostatectomy specimen findings, potential biochemical failure, local recurrences, lymph nodes or distant metastases in patients not receiving any treatment as well as those receiving treatment including radiation therapy, surgical treatment such as radical prostatectomy and other therapies etc,. However, characterisation and classification of prostate cancer is very different compared to 40-50 years ago when Gleason scores were first introduced. Despite this radical shift in classification, the Gleason system has remained one of the most important prognostic factors in prostate cancer, only possible as a result of timely and appropriate modifications to this characterisation system made in 2005 and 2014. However, even after these modifications, certain limitations of the Gleason system remain, due to which a new prostate cancer prognostic grade group system was introduced in 2014, which was widely accepted in the 2014 ISUP consensus conference, and incorporated into the WHO classification of thetumor of the Urinary System and Male Genital Tract in 2016. Herein, this article will discuss how this new prognostic grade group system, which is regarded as simpler and more accurate than the Gleason system risk stratification groups, will be used in conjunction with the Gleason system to improve patient prognosis and treatment.

Chaudhary S, Islam Z, Mishra V, et al.
Sox2: A Regulatory Factor in Tumorigenesis and Metastasis.
Curr Protein Pept Sci. 2019; 20(6):495-504 [PubMed] Related Publications
The transcription factor Sox2 plays an important role in various phases of embryonic development, including cell fate and differentiation. These key regulatory functions are facilitated by binding to specific DNA sequences in combination with partner proteins to exert their effects. Recently, overexpression and gene amplification of Sox2 has been associated with tumor aggression and metastasis in various cancer types, including breast, prostate, lung, ovarian and colon cancer. All the different roles for Sox2 involve complicated regulatory networks consisting of protein-protein and protein-nucleic acid interactions. Their involvement in the EMT modulation is possibly enabled by Wnt/ β-catenin and other signaling pathways. There are number of in vivo models which show Sox2 association with increased cancer aggressiveness, resistance to chemo-radiation therapy and decreased survival rate suggesting Sox2 as a therapeutic target. This review will focus on the different roles for Sox2 in metastasis and tumorigenesis. We will also review the mechanism of action underlying the cooperative Sox2- DNA/partner factors binding where Sox2 can be potentially explored for a therapeutic opportunity to treat cancers.

Al-Khodir FAI, Abumelha HMA, Al-Warhi T, Al-Issa SA
New Platinum(IV) and Palladium(II) Transition Metal Complexes of s-Triazine Derivative: Synthesis, Spectral, and Anticancer Agents Studies.
Biomed Res Int. 2019; 2019:9835745 [PubMed] Free Access to Full Article Related Publications
New Pd(II) and Pt(IV) triazine complexes [Pt

Fan W, Lu N, Shen Z, et al.
Generic synthesis of small-sized hollow mesoporous organosilica nanoparticles for oxygen-independent X-ray-activated synergistic therapy.
Nat Commun. 2019; 10(1):1241 [PubMed] Free Access to Full Article Related Publications
The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)

Alyabsi M, Charlton M, Meza J, et al.
The impact of travel time on colorectal cancer stage at diagnosis in a privately insured population.
BMC Health Serv Res. 2019; 19(1):172 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Rural residents are less likely to receive screening for colorectal cancer (CRC) than urban residents. However, the mechanisms underlying this disparity, especially among people aged 50-64 years old with private health insurance, are not well understood. We examined the impact of travel time on stage at CRC diagnosis.
METHODS: This retrospective cohort study used data from the Blue Cross and Blue Shield of Nebraska. Members of this private insurance company aged 50-64 years, diagnosed with CRC during the period 2012-2016, and continuously enrolled in the insurance plan for at least 6 months prior to CRC diagnosis, were selected for this study. Using Google Maps, we estimated patients' travel time from their home ZIP code to the ZIP code of their colonoscopy provider. Using logistic regression, we analyzed the association between stage at CRC diagnosis, travel time, use of preventive services (i.e., check-ups or counseling to prevent or detect illness at an early stage) and patient characteristics.
RESULTS: A total of 307 subjects met the inclusion criteria. People who had not used preventive services 6 months prior to CRC diagnosis had 2.80 (95% CI, 1.00-7.90) times the odds of metastatic CRC compared to those who had used these services. No statistically significant association was found between travel time and metastatic CRC diagnosis (P = 0.99; 95% CI, 0.98-1.01).
CONCLUSIONS: The fact that 13% of the study population presented with metastatic CRC suggests some noncompliance with preventive services such as screening guidelines. To increase screening uptake and reduce metastatic cases, employers should offer incentives for their employees to make use of preventive services such as CRC screening.

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