Epstein-Barr virus infection mediated TP53 and Bcl-2 expression in nasopharyngeal carcinoma pathogenesis.

Epstein Barr virus (EBV) stimulates neoplastic transformation of nasopharyngeal epithelial cells through various molecular mechanisms, predominantly affecting inactivation of tumor-suppressor genes and activation of oncogenes. EBV infection is a major risk factor for nasopharyngeal carcinoma (NPC), yet its role in the carcinogenesis is not clear. EBV infection alters the expression of antiapoptotic proteins and tumor suppressor proteins. Therefore, this study investigated the correlation between EBV infection status with B cell lymphoma-2 (Bcl-2) and TP53 protein expression amongst laryngeal and nasopharyngeal cancer cases. This study was performed using 22 nasopharyngeal and 11 laryngeal cancer cases. EBV infection status, TP53 and Bcl-2 protein expression was studied using immunohistochemistry. The majority of the laryngeal cancer cases exhibited a poor prognosis and presented low Bcl-2 expression. A total of 22.7% cases were infected with EBV in the NPC cases. Upregulated TP53 expression was associated with EBV infection in the NPC cohort, and EBV infection was correlated with TP53 upregulation in the patients with NPC, suggesting mutual regulation between TP53 and EBV.

Knowledge, Attitude and Practice Regarding Risk of Diabetic Foot Among Diabetic Patients in Aseer Region, Saudi Arabia.

Background Diabetic foot care is vital as it is preventable complication but dangerous even a small trauma can end with serious consequences. Diabetes may cause nerve damage that affects feet sensation. Diabetes may also reduce blood flow to the feet, making it harder to heal an injury or resist infection. Because of these problems, patients may lose notice of early foot abnormalities. Diabetic patients' awareness regarding how to care for their feet plays a significant role in preventing these complications. Methods A correlation cross-sectional study was conducted targeting all diabetic patients aging 20 years or more. Online questionnaire was used for data collection. Questionnaire was uploaded online using social media platforms by the researchers and their relatives and friends. The questionnaire included patient personal data, patients' knowledge regarding diabetic foot, attitude and practice regarding the risk of diabetic foot among diabetic patients. Results A total of 1,000 diabetic patients fulfilling the inclusion criteria completed the study questionnaire. Exact of 77.5% of the patients know that Diabetics can get gangrene in the foot, 74.9% know diabetics can develop ulcers in the foot, 66.7% reported that Diabetes can reduce blood flow to the feet of diabetic patients, 66.6% agreed that diabetic patients can suffer from a lack of sensation in the feet. Exact of 84.5% of the study participants agreed that Diabetics should check for any wounds on their feet daily, 78.7% agreed that Diabetics should visit a doctor when there is any infection or wound in the feet, 76.6% think that diabetic patients should wear specialized shoes to avoid diabetic foot according to the doctor's instructions. A total of 822 (82.2%) of the study patients wash their feet daily, and 295 (29.5%) usually wear cotton socks regularly and 39.6% sometimes wear the stock. Only 192 (19.2%) regularly walk barefoot and 41.7% sometimes do. Conclusion In conclusion, the current study results showed that nearly two out of each three diabetic patients were knowledgeable for diabetic foot and its care. High knowledge was associated with young age, high education and having family member with diabetes mellitus (DM). Also, patients had a good attitude towards diabetic foot care and the effect of diabetes on foot health with to some level accepted practice except for some issues.

RNA sequencing-based identification of potential targets in acute myeloid leukemia: A case report.

Acute myeloid leukemia (AML) refers to heterogenous types of blood cancer which possess a complicated genomic landscape, and multiple novel mutational alterations are frequently being reported. Herein, a case report of a 37-year old AML patient is presented, who was diagnosed following laboratory investigation after admission. The patient had thrombocytopenia, and three consecutive blast counts of 40, 30 and 41%, respectively. A blood sample was collected for whole-genome RNA sequencing to understand the transcriptomic profile at the time of diagnosis and compared with a matched female control. Gene expression was quantified using the RSEM software package. Bioinformatics analysis revealed a significant number of differentially expressed genes in the patient, suggesting a marked change in the transcriptomic landscape in this patient. By mining the bioinformatics data and screening the highly expressed genes with ≥80% probability of gene expression, four novel genes were highlighted that may serve as potential future targets in AML patients; Rh associated glycoprotein, succinate receptor 1, transmembrane-4 L-six family member-1 and ADGRA3, although further validation of their value is required.

Association of epidermal growth factor receptor protein expression with histopathological and clinical parameters in carcinoma of the larynx.

BACKGROUND: Laryngeal cancer is one of the most commonly occurring cancers in head and neck malignancies with the majority of tumors being squamous cell carcinomas. Despite sharing similarities with other head and neck tumors, laryngeal tumors require a special approach in treatment due to the need for organ preservation. Non-surgical procedures, including chemotherapy, radiotherapy and novel targeted therapies are alternative options. However, the selection of appropriate treatment modality is crucial for recurrence-free survival. With the availability of targeted therapies, the biomarker expression pattern has become a vital tool in the selection of treatment and prognosis. The present study aims to study the variation of protein [epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN) and p16INK4] expression and human papillomavirus (HPV) infection status in larynx carcinoma patients and correlate it with histopathological and clinical parameters. METHODS: This is a retrospective study comprising laryngeal carcinoma tumor samples from 18 patients. The samples were analyzed for EGFR, PTEN and p16INK4 expression by immunohistochemistry and HPV status by chromogenic in-situ hybridization (CISH). RESULTS: The EGFR over expression was observed in the 83.3% of patients. This high EGFR expression was associated with lymph node positivity (P=0.045) and advanced disease stage (P=0.035). Furthermore, the smoking status of the patients is correlated with a better prognosis (P=0.048). The PTEN was negatively expressed in 94.4% patients. CONCLUSIONS: The association of EGFR over expression with lymph node status and advanced stage of the disease supports the role that EGFR plays in the tumor metastasis and invasion in laryngeal carcinoma patients. Therefore, the use of anti-EGFR targeted therapy in cases of laryngeal carcinoma may improve the prognosis of these patients. The other studied proteins p16INK4, PTEN and HPV infection did not show any correlation with prognosis and other clinical parameters.

Outcome of Chronic Myeloid Leukemia-Chronic Phase Patients Treated With Imatinib: A Local Experience.

BACKGROUND: Imatinib was the first tyrosine kinase inhibitor that has revolutionized the therapy of chronic myeloid leukemia. It binds breakpoint cluster region-Abelson kinase domain inducing apoptosis of the leukemic cells. In this study, we assessed the efficacy and toxicity of imatinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) in our hospital. PATIENTS AND METHODS: We retrospectively analyzed the outcome of 17 patients with CML-CP treated with imatinib. RESULTS: The median age at the time of presentation was 35 years with male preponderance. The most common presenting clinical features were fatigue, abdominal distention, and discomfort. Forty-seven percent of patients had fever at presentation whereas 35.29% were referred to our hospital because of incidental findings of high blood cell counts. With a median follow-up of 8 years (range, 2-16 years) the overall survival is 100% and progression-free survival 85%. Two patients had acceptable adverse effects. CONCLUSION: After a median follow-up of 8 years, imatinib was found to induce long survival with manageable side effect in adult Saudi patients with CML-CP.

Tyrosine kinase domain mutations of EGFR gene in head and neck squamous cell carcinoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) is a commonly altered gene that is identified in various cancers, including head and neck squamous cell carcinoma (HNSCC). Therefore, EGFR is a promising molecular marker targeted by monoclonal antibodies and small molecule inhibitors targeting the tyrosine kinase (TK) domain. OBJECTIVE: The objective of this study was to investigate the spectrum of mutations in exons 18, 19, 20, and 21 of the EGFR gene in HNSCC patients. MATERIALS AND METHODS: This retrospective study included 47 confirmed HNSCC cases. Mutations in the TK domain, exons 18, 19, 20, and 21 of the EGFR gene, were detected by Scorpion® chemistry and ARMS® technologies on Rotor-Gene Q real-time polymerase chain reaction. RESULTS: The tumors exhibited EGFR-TK domain mutations in 57% of cases. Four cases of T790M mutations were reported for the first time among HNSCC patients. Out of the total mutations, L861Q (exon 21), exon 20 insertions and deletions of exon 19 accounted for the majority of mutations (21%, 19%, and 17%, respectively). EGFR mutation status was correlated with the higher grade (P=0.026) and advanced stage (P=0.034) of HNSCC tumors. CONCLUSION: Higher frequency of EGFR-TK domain mutations together with the presence of the T790M mutation suggests that identification of these mutations might streamline the therapy and provide a better prognosis in HNSCC cases.

Sudden Visual Loss as an Initial Manifestation of Chronic Myeloid Leukemia.

Chronic myelogenous leukemia (CML) is a pluripotent stem cell disease characterized by anemia, granulocytosis and granulocytic immaturity, basophilia, thrombocytosis and splenomegaly. It is associated with a reciprocal chromosomal translocation t (q34; q11), resulting in a breakpoint cluster region-Abelson fusion gene (Philadelphia chromosome). Ophthalmic manifestations as the first and the only presentation of CML in patients are very rare. Ocular lesions in CML patients are frequently asymptomatic, and thus all patients should undergo an eye evaluation at the initial diagnosis. Here, we report a previously healthy 36-year-old Saudi male who initially presented with progressive loss of vision. On examination, he was found to have a bilateral retinal hemorrhage. The investigations revealed findings consistent with CML. The patient was treated with tyrosine kinase inhibitors, and he had complete remission, including full recovery of his vision.

Novel mutations of PIK3CA gene in head and neck squamous cell carcinoma.

BACKGROUND: HNSCC is the sixth most common human cancer globally. In Saudi Arabia, HNSCC accounts for seven percent of all newly diagnosed cancer cases. The PIK3CA is one of the most commonly mutated oncogene in human malignancies, including HNSCC. OBJECTIVE: The objective of this study is to identify mutations in exon 9 and exon 20 of the PIK3CA gene among Saudi HNSCC patients, determine the frequency of these mutations and correlate with clinical and pathological findings. METHODS: Histopathologically confirmed paraffin embedded HNSCC tumor tissues from 48 patients were obtained. Capillary sequencing method was used to sequence exons 9 and 20 of the PIK3CA gene. Concurrently, the expression analysis of the PIK3CA and PTEN genes were performed using real-time PCR. RESULTS: Sixty percent of the samples studied were of pharyngeal cancer. A total of seven mutations were identified in exons 9 and 20 of the PIK3CA gene in 14 HNSCC tumor tissue specimens. The seven mutations encompassed one hot spot mutation E542K, a common mutation T1025T and the five novel mutation comprising three missense and two silent mutations. Interestingly, eight out of the 14 samples with a mutation were of patients with pharyngeal cancer. CONCLUSION: PIK3CA gene plays a crucial role in carcinogenesis in general and HNSCC in particular. The identification of five novel mutations suggest that Saudis may have different frequencies of somatic genetic alterations that may influence HNSCC compared to other populations.

Clinical presentation and causes of the delayed diagnosis of breast cancer in patients with pregnancy associated breast cancer.

OBJECTIVE: The objective was to assess the clinical presentation, delay of diagnosis, and the causes of delay in the diagnosis of patients with pregnancy-associated breast cancer (PABC) and patients with non-PABC. PATIENTS AND METHODS: This was a face-to-face interview with women who had histologically confirmed BC. All respondents were interviewed at our hospital. RESULTS: We interviewed 56 patients, 36 with non-PABC and 20 with PABC. Of the 20 patients with PABC, BC was diagnosed in 12 (60%) during pregnancy and 8 (40%) during postpartum. 18 of the patients (90%) with PABC presented mainly with a mass 3 (15%) with pain and ulcer, 5 (25%) with skin redness and thickening, 6 (30%) with nipple retraction and 4 (20%) with discharge 12 (60%) patients with PABC had delayed diagnosis and 8 (40%) of this delay was due to physicians' reassurance, and 2 (10%) because of fear of cancer. Similarly, 35 (97%) patients with non-PABC presented with breast mass, 3 (8.3%) with infrequent pain 4 (11.11%) with inflammation 2 (5.55%) with ulcer 2 (5.55%) with nipple discharge and4 (11.11%) with thickening of the skin compared with PABC patients. Only 4 (11.11%) in non-PABC had delayed diagnosis, and for half of them the delay was due to the fear of cancer. Two patients with PABC and non-PABC were afraid of cancer 16.66% and 5.55%, respectively. However, 8 (60%) of patients with PABC had delayed diagnosis compared to 0% of patients with non-PABC. CONCLUSION: In this study, the majority of patients with PABC or non-PABC presented with a breast lump. Other symptoms were more common in patients with PABC than in patients with non-PABC. An increased awareness of clinicians may help reduce delay in the diagnosis of patients with PABC.

Future Saudi doctors and cancer patients agree cancer patients should be informed about their cancer.

AIM: To compare attitudes of Saudi medical students and Saudi cancer patients towards disclosure of cancer information and to examine whether differences exist between students and patients, level of education or gender and region of residence. METHODS: Data were collected from 384 students and 368 patients using a nine-question questionnaire on attitudes to cancer. RESULTS: Almost all patients (98%) wanted to receive all the information should they get cancer compared with 93% of students (P = 0.001) and almost no patients and students wanted the information hidden (99 vs 98%, P = 0.273). If they became ill students were more likely to share information with their family and friends than patients. Fewer than 2% of patients did not want to know the benefits of chemotherapy compared to 3% of students, while 99% of patients wanted to know the side-effects compared to 93% of students (P = 0.095 and P = 0.001, respectively). Almost all patients and students (99 vs 98%) would refuse treatment without knowing their diagnosis (P = 0.401). Patients wanted to know the prognosis more than students (98 vs 92%; P = 0.001). In all, 99% of male students wanted their cancer diagnosis disclosed compared with women (98%; P = 0.615). Gender, education level, regions and age did not affect the desire of cancer patients to know their prognosis (P = 0.275, P = 0.664, P = 0.0314 and P = 0.164, respectively). CONCLUSION: There was a consensus among cancer patients and medical students that cancer information, including diagnosis, treatment effects and prognosis, should be disclosed to patients.

Castleman disease.

Castleman and Towne described a disease presenting as a mediastinal mass resembling thymoma. It is also known as "giant lymph node hyperplasia", "lymph node hamartoma", "angiofollicular mediastinal lymph node hyperplasia", and "angiomatous lymphoid hyperplasia". The pathogenesis is unknown, but the bulk of evidence points toward faulty immune regulation, resulting in excessive B-lymphocyte and plasma-cell proliferation in lymphatic tissue. In addition to the mediastinal presentation, extrathoracic involvement in the neck, axilla, mesentery, pelvis, pancreas, adrenal gland, and retroperitoneum also have been described. There are 2 major pathologic variations of Castleman disease: (1) hyaline-vascular variant, the most frequent, characterized by small hyaline-vascular follicles and capillary proliferation; and (2) the plasma-cell variant, in which large lymphoid follicles are separated by sheets of plasma cells. The hyaline-vascular cases usually are largely asymptomatic, whereas the less common plasma-cell variant may present with fever, anemia, weight loss, and night sweats, along with polyclonal hypergamma-globulinemia. Castleman disease is a rare lymphoproliferative disorders. Few cases have been described world widely. In this article we reviewed the classification, pathogenesis, pathology, radiological features and up to date treatment with special emphasis on the role of viral stimulation, recent therapeutic modalities and the HIV-associated disease.

Cellular and molecular responses of Saudi chronic myeloid leukaemia patients to imatinib (STI-571): ten year experience.

BACKGROUND: The cyto-genetic hallmark of chronic myeloid leukaemia (CML), the Philadelphia chromosome (Ph), is the first consistent chromosomal abnormality that has been associated to a certain cancer type. In CML, Philadelphia chromosome is present leading to resistance to cell death and rapid proliferation. The aim of this study is to evaluate the different responses, toxicity and survival of Saudi CML patients to imatinib mesylate. METHODS: All newly diagnosed CML patients who were treated with imatinib were included in this study. We investigated haematological, and molecular and cytogenetic responses by CBC, FISH and RT-PCR respectively. Cell proliferation and apoptosis were assayed using AUC and TUNEL respectively. RESULTS: Of the 12 cases, 9 (75%) were males and 3 (25%) were female. Four (33%) of the cases were diagnosed incidentally and 8 cases (67%) presented mainly with fatigue (75%), fever (58%), and splenomegaly (83%). Signs of bleeding and rashes were rare at presentation. The majority of patients had low risk (8, 67%), and 33% had intermediate risk; but none of them had high risk CML. At the last follow up, 11 (92%) were in remissions. One patient (8%) was in remission after 3 years, 4 (33%) were in remission after 6 years, one was in remission after 7 years and 5 (42%) were in remission after 10 years. Only one patient had incomplete major molecular response (MMR) to imatinib after 12 years. The majority of the patients (10, 83%) were in MMR after 6 years and 42% of them were in MMR after 10 years of therapy. Adverse effects of imatinib were not reported by the patients. Imatinib treatment resulted in the reduction of proliferation and induction of apoptosis of CML CFU-GM cells. CONCLUSION: Imatinib mesylate is capable of treating Philadelphia chromosome-positive CP-CML without any adverse effects.

Attitudes of Saudi medical students toward the disclosure of information on cancer in eastern Saudi Arabia.

OBJECTIVE: To assess the attitude of future physicians regarding the disclosure of diagnosis, prognosis, benefits, and adverse effects of therapeutic intervention if they happen to have cancer. It also examined the differences if any between regions or gender. MATERIALS AND METHODS: A total of 332 medical students from University of Dammam, in the Eastern Province of the Kingdom of Saudi Arabia were surveyed using a self-administered questionnaire. The questionnaire consisted of nine questions on the attitudes to disclosure of information on cancer. This self-administered questionnaire was completed by the students in the presence of an investigator. RESULTS: The vast majority of Saudi medical students stated that they would like to know about diagnosis of cancer (92.8%) and only 7.2% wanted information withheld from them. Further, 67% of the males and 74.1% of the females wanted family members to know (P = 0.01), but one-third (33%) did not want their family to know. Only 24.1% of the male and 21.1% of female students wanted their friends to know. In addition, -97% of the males and 98.8% of the females wanted to know the diagnosis, and 97% and 95.8% of females and males, respectively, would like to know the side effects of the therapy. Almost 95% of male and 93.4% of female students wanted to know the prognosis. Also, 98% of medical students from the Eastern Region would want the diagnosis of cancer to be disclosed compared to 73.6% of those from other regions (P = 0.01). There is no difference between the genders in attitudes toward the disclosure of the diagnosis, 94.6% and 92.2% (P = 0.38). CONCLUSIONS: There was a consensus among Saudi medical students on the knowledge of the benefits of treatment, adverse effects of therapy, and prognosis. Female students significantly more than males would like their families to be informed. Significantly more medical students from the Eastern Region than those from other regions would like the diagnosis of cancer to be disclosed.

Long-Term Survival of Gastric Adenocarcinoma without Therapy: Case Report.

Planning for treatment of gastric adenocarcinoma in a patient previously treated with partial gastrectomy for primary gastric lymphoma is difficult. Long term survival of advanced gastric adenocarcinoma is poor with therapy and even worse without treatment. The only potentially curative treatment for gastric adenocarcinoma is surgical resection with adequate margins. Palliative surgery ameliorate symptoms in about 50% of patients Chemotherapy may play a lesser role. This report presents a case of gastric adenocarcinoma in a patient who had primary gastric lymphoma treated with partial gastrectomy. The patient is still alive 6 years after diagnosis with no signs of progression despite the fact that no active treatment was given.

Distribution of molecular breast cancer subtypes in middle eastern-saudi arabian women: a pilot study.

Increasing evidence suggests the possibility of relevant molecular differences between cancers from different ethnic groups. This study uses gene expression profiling by quantitative real time polymerase chain reaction (qRT-PCR) to identify "intrinsic" subtypes in a Saudi population of breast cancers and compares the distribution of subtypes to the more commonly profiled Caucasian population. In addition, the immunohistochemical profile of breast cancers was correlated to the gene expression analysis. Discrepancy rate of 39% in subtype prediction between gene expression and immunohistochemical profile of the tumors was noticed. Most of this variation was in the luminal subtype. Frequency of HER2+ subtype in the Saudi cases was high (28%) by both the immunohistochemistry (IHC) and the qRT-PCR classification. Triple-negative tumors comprised 39% while only 11% showed a basal-like profile. Analysis of larger cohort of patients is needed to determine the molecular taxonomy of breast cancer in the Saudi population and the benefits from the diagnostic classification developed in the West.

Prevention of breast cancer.

The best therapy for cancer is prevention. Primary prevention involves health promotion and risk reduction in the general population so that invasive cancers do not develop. These primary preventive measures include the cessation of smoking, lifestyle and diet modification, vitamins and micronutrients supplementation. Identification of genetic risk, understanding of carcinogenesis, development of effective screening tools, avoiding risk factors and effective chemoprevention can lead to decreased morbidity and mortality of cancers in general and more importantly breast cancer. Secondary prevention is the identification and treatment of premalignant or subclinical cancers. Screening by means of mammography is a typical example of secondary prevention. Tertiary prevention is defined as symptoms control and rehabilitation. These definitions may become less useful in the future as they do not account for the new incoming data such as molecular data.