The Complex Connection between Obesity and Cancer: Signaling Pathways and Therapeutic Implications.

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/ß-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

Dual-loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer.

INTRODUCTION: The resistance to chemotherapy is a significant hurdle in breast cancer treatment, prompting the exploration of innovative strategies. This review discusses the potential of dual-loaded liposomal carriers to combat chemoresistance and improve outcomes for breast cancer patients. AREAS COVERED: This review discusses breast cancer chemotherapy resistance and dual-loaded liposomal carriers. Drug efflux pumps, DNA repair pathways, and signaling alterations are discussed as chemoresistance mechanisms. Liposomes can encapsulate several medicines and cargo kinds, according to the review. It examines how these carriers improve medication delivery, cancer cell targeting, and tumor microenvironment regulation. Also examined are dual-loaded liposomal carrier improvement challenges and techniques. EXPERT OPINION: The use of dual-loaded liposomal carriers represents a promising and innovative strategy in the battle against chemotherapy resistance in breast cancer. This article has explored the various mechanisms of chemoresistance in breast cancer, emphasizing the potential of dual-loaded liposomal carriers to overcome these challenges. These carriers offer versatility, enabling the encapsulation and precise targeting of multiple drugs with different modes of action, a crucial advantage when dealing with the complexity of breast cancer treatment.

PTEN, ERG, SPINK1, and TFF3 Status and Relationship in a Prostate Cancer Cohort from Jordanian Arab Population.

Background and Objectives: Prognostic biomarkers in prostate cancer (PCa) include PTEN, ERG, SPINK1, and TFF3. Their relationships and patterns of expression in PCa in developing countries, including Jordan, have not yet been investigated. Materials and Methods: A tissue microarray (TMA) of PCa patients was taken from paraffin-embedded tissue blocks for 130 patients. PTEN, ERG, SPINK1, and TFF3 expression profiles were examined using immunohistochemistry (IHC) and correlated with each other and other clinicopathological factors. Results: PTEN loss of any degree was observed in 42.9% of PCa cases. ERG and TFF3 were expressed in 59.3% and 46.5% of PCa cases, respectively. SPINK1 expression was observed in 6 out of 104 PCa cases (5.4%). Among all PCa cases (n = 104), 3.8% (n = 4) showed SPINK1+/ERG+ phenotype, 1.9% (n = 2) showed SPINK1+/ERG- phenotype, 56.7% (n = 59) showed SPINK1-/ERG+ phenotype, and 37.5% showed SPINK1-/ERG- phenotype (n = 39). Among ERG positive cases (n = 63), 6.3% were SPINK1 positive. Among SPINK1 positive cases (n = 6), 66.7% were ERG positive. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3 (6/6). Additionally, a statistically significant loss of PTEN expression was observed from Gleason Score 6 (GS6) (Grade Group 1 (GG1)) to GS9-10 (GG5); (p-value 0.019). Conclusions: This is the first study to look at the status of the PTEN, ERG, SPINK1, and TFF3 genes in a Jordanian Arab population. Loss of PTEN has been linked to more aggressive prostate cancer with high GSs/GGs. SPINK1 expression was predominantly observed in a subgroup of cancers that expressed TFF3. Our results call for screening these biomarkers for grading and molecular subtyping of the disease.

The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia.

Chronic Myeloid Leukemia (CML) is characterized by chromosomal aberrations involving the fusion of the BCR and ABL genes on chromosome 22, resulting from a reciprocal translocation between chromosomes 9 and 22. This fusion gives rise to the oncogenic BCR-ABL, an aberrant tyrosine kinase identified as Abl protein. The Abl protein intricately regulates the cell cycle by phosphorylating protein tyrosine residues through diverse signaling pathways. In CML, the BCR-ABL fusion protein disrupts the first exon of Abl, leading to sustained activation of tyrosine kinase and resistance to deactivation mechanisms. Pharmacological interventions, such as imatinib, effectively target BCR-ABL's tyrosine kinase activity by binding near the active site, disrupting ATP binding, and inhibiting downstream protein phosphorylation. Nevertheless, the emergence of resistance, often attributed to cap structure mutations, poses a challenge to imatinib efficacy. Current research endeavours are directed towards overcoming resistance and investigating innovative therapeutic strategies. This article offers a comprehensive analysis of the structural attributes of BCR-ABL, emphasizing its pivotal role as a biomarker and therapeutic target in CML. It underscores the imperative for ongoing research to refine treatment modalities and enhance overall outcomes in managing CML.

Mature cystic teratoma of the ovary with malignant transformation of tall cell subtype of papillary thyroid carcinoma.

Malignancies rarely occur in somatic parts of mature cystic teratoma of the ovary. Squamous cell carcinoma is the most common form of cancer that can develop in mature cystic teratoma. Other less frequent malignancies include melanoma, sarcoma, carcinoid, and germ cell neoplasms. Only three cases have been reported as papillary thyroid carcinoma arising in struma ovarii. We present a unique case of a 31-year-old female patient who presented with a left ovarian cyst and underwent conservative surgical management in the form of cystectomy. Histopathological examination confirmed the diagnosis of a tall cell subtype of papillary thyroid carcinoma arising from a small focus of thyroid tissue in a mature cystic teratoma of the ovary. The patient was followed up for 60 months with an uneventful clinical course. For a better understanding of such rare cancers, collaborative retrospective studies on large databases with other medical centers are required.

Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.

PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes. PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS). CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.

Impact of exosome therapy on pancreatic cancer and its progression.

Pancreatic cancer, one of the most aggressive tumors, has a dismal prognosis because of the low rates of early identification, fast progression, difficulties following surgery, and the ineffectiveness of current oncologic therapies. There are no imaging techniques or biomarkers that can accurately identify, categorize, or predict the biological behavior of this tumor. Exosomes are extracellular vesicles that play a crucial rule in the progression, metastasis, and chemoresistance of pancreatic cancer. They have been verified to be potential biomarkers for pancreatic cancer management. Studying the role of exosomes in pancreatic cancer is substantial. Exosomes are secreted by most eukaryotic cells and participated in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long non-coding RNA, circular RNA, etc., play a crucial role in regulating tumor growth, metastasis, and angiogenesis in the process of cancer development, and can be used as a prognostic marker and/or grading basis for tumor patients. Hereby, in this concise review, we intend to summarize exosomes components and isolation, exosome secretion, function, importance of exosomes in the progression of pancreatic cancer and exosomal miRNAs as possible pancreatic cancer biomarkers. Finally, the application potential of exosomes in the treatment of pancreatic cancer, which provides theoretical supports for using exosomes to serve precise tumor treatment in the clinic, will be discussed.

A Genetic and Immunohistochemical Analysis of Helicobacter pylori Phenotypes and p27 Expression in Adenocarcinoma Patients in Jordan.

Stomach (gastric) cancer is one of the most prevalent and deadly cancers worldwide and most gastric cancers are adenocarcinomas. Based on prior research, there is an association between Helicobacter pylori (H. pylori) infection together with the frequency of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and antral gastritis. Helicobacter pylori virulence and toxicity factors have been identified before that significantly influence the clinical outcomes of H. pylori infection and gastric adenocarcinoma. However, it remains unclear exactly how different strains of H. pylori affect gastric adenocarcinoma. Current research suggests this involves tumor suppressor genes, like p27 but also H. pylori toxic virulence proteins. Therefore, we quantified known H. pylori genotypes within adenocarcinoma patients to establish the prevalence of known toxins that include cytotoxin-associated gene A (cagA) as well as vacuolating cytotoxin A (vacA) within patients of variable adenocarcinoma diagnosis. This analysis used gastrectomy samples validated for DNA viability. The incidence of H. pylori in adenocarcinoma patients in Jordan was established to be 54.5% positive (ureA gene positive) with cagA genotype occurrence at 57.1%, but also in this population study vacA gene ratios found to be 24.7%:22.1%:14.3%:14.3%. (vacAs1:vacAs2:vacAm1:vacAm2). Using immunohistochemistry (IHC), we confirmed with statistical significance that p27 was dysregulated and suppressed, within nearly all H. pylori vacA genotypes. In addition, within 24.6% of H. pylori samples analyzed was a different bacterial genotype, and curiously that p27 protein expression was retained in 12% of tested adenocarcinoma H. pylori samples. This is suggestive that p27 could be used as a prognostic indicator but also that an unknown genotype could be contributing to the regulatory effects of p27 protein within this bacterial and cellular environment that may include other virulence factors and unknown immune system regulatory changes.

Soft Tissue Sarcomas: A 16-Year Experience of a Tertiary Referral Hospital in North Jordan.

Background and Objectives: Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods: All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results: In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR)(World WHO 2000-2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion: STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.

A 47-Year-Old Woman with Immunoglobulin G4 (IgG4)-Related Disease Involving the Right Ovary.

BACKGROUND Immunoglobulin G4 (IgG4)-related disease is immune-mediated and was first proposed as a defined entity after studies on patients with autoimmune pancreatitis. Since then, it has been reported in many organs. Involvement of the ovaries is rare, and to our knowledge, only 2 cases have been reported in the literature. IgG4-related disease is associated with increased serum IgG4 levels. Organ involvement includes a lymphoplasmacytic infiltrate, fibrosis, and obliterative phlebitis, with immunohistochemistry showing IgG4-positive plasma cells. This report is of a case of IgG4-related disease involving the right ovary. CASE REPORT A 47-year-old woman presented with a right ovarian cyst. An ultrasound scan revealed a complex right ovarian cyst with multiple septations. The hormonal profile and tumor markers were unremarkable. Gross examination showed fragments of cyst wall. Histologic examination revealed a follicular cyst, surrounded by a dense lymphoplasmacytic infiltrate rich in eosinophils, partially obliterative phlebitis, and fibrosis. Immunohistochemically, IgG marked most of the plasma cells, of which 70% expressed IgG4, with a count >50 cells per high-power field. Subsequent testing of serum IgG4 showed that the level was elevated (330 mg/dL). A diagnosis of IgG4-related disease was made. CONCLUSIONS Ovarian involvement by IgG4-related disease is rarely described in the literature. Our patient is likely to be the third case. We believe that cumulative findings from our case along with the 2 already reported cases increase awareness and may establish a framework for building more objective criteria to define this entity in the ovaries, similar to what has been achieved in some other organs.

Impact of Obesity on Clinicopathologic Characteristics and Disease Prognosis in Pre- and Postmenopausal Breast Cancer Patients: A Retrospective Institutional Study.

Purpose: To investigate the association between obesity and breast cancer clinicopathologic characteristics at presentation along with prognostic impact among Jordanian breast cancer patients. Such data are lacking in Arabian countries. Methods: In this retrospective study, 348 breast cancer patients were included. Analyses were conducted for associations between body mass index (BMI) and age at diagnosis, tumor clinicopathologic characteristics, and molecular subtypes. Eight prognostic factors were considered, and total prognostic scores were calculated. The analysis was stratified by menopausal status. Multivariate logistic stepwise regression analysis was conducted to identify predictors for breast cancer recurrence and death. Results: Mean age at diagnosis was 50.98 ± 10.96 years. Mean BMI at diagnosis was 29.52 ± 5.32 kg/m2. Mean age at diagnosis was significantly higher for overweight and obese patients compared to underweight/normal patients (P < 0.001). A significant positive correlation was observed between patient age and BMI at diagnosis (r = 0.251, P < 0.001). Grade of carcinoma was significantly correlated with BMI in the whole population examined (P=0.003). Obese breast cancer patients had significantly higher prognostic scores compared to nonobese cases, indicating worse prognostic features at presentation (P=0.034). Stratification of data analysis based on menopausal status revealed significant associations between obesity and each of tumor stage and grade among postmenopausal but not premenopausal patients (P=0.019 and P=0.031, respectively). Similarly, postmenopausal obese patients had significantly higher prognostic scores compared to nonobese counterparts (P=0.007), indicating worse prognosis, a finding which was also absent among premenopausal breast cancer patients. No significant association between BMI with expression status of hormone receptors, HER2, lymphovascular invasion, and molecular subtypes was found among patients. BMI was a significant predictor for disease recurrence in which obese breast cancer patients had greater odds (2-fold) to develop locoregional and distant recurrence compared to nonobese cases (P=0.011). Conclusions: Obesity was associated with advanced stage and grade of breast carcinoma at diagnosis. The impact of BMI on clinicopathologic characteristics and prognosis was confined to postmenopausal cases. Jordanian obese breast cancer patients are at greater risk of breast cancer recurrence and reduced survival compared to their nonobese counterparts.

A novel approach for quantitative assessment of mucosal damage in inflammatory bowel disease.

AIMS: One of the main reliable histological features to suggest the diagnosis of inflammatory bowel disease is the presence of significant distortion of the crypt architecture indicating the chronic nature of the disease resulting in mucosal damage. This feature has a considerable intra-observer and inter-observer variability leading to significant subjectivity in colonic biopsy assessment. In this paper, we present a novel automated system to assess mucosal damage and architectural distortion in inflammatory bowel disease (IBD). METHODS: The proposed system relies on advanced image understating and processing techniques to segment digitally acquired images of microscopic biopsies, then, to extract key features to quantify the crypts irregularities in shape and distribution. These features were used as inputs to an artificial intelligent classifier that, after a training phase, can carry out the assessment automatically. RESULTS: The developed system was evaluated using 118 IBD biopsies. 116 out of 118 biopsies were correctly classified as compared to the consensus of three expert pathologists, achieving an overall precision of 98.31%. CONCLUSIONS: An automated intelligent system to quantitatively assess inflammatory bowel disease was developed. The proposed system utilized advanced image understanding techniques together with an intelligent classifier to conduct the assessment. The developed system proved to be reliable, robust, and minimizes subjectivity and inter- and intra-observer variability. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1797721309305023.

Antioxidant activity of simvastatin prevents L-arginine-induced acute toxicity of pancreas.

L-arginine is a semi-essential amino acid that found naturally in food. It has been shown that administration of large doses of L-arginine can induce acute pancreatitis. In the present study, we evaluated if simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, might prevent acute pancreatitis induced by L-arginine. Thirty male Wistar rats were randomly allocated to five groups. Groups were: DMSO, saline, simvastatin, L-arginine, and simvastatin with L-arginine. Twenty four hours after the last dose, rats were sacrificed and their blood was collected from heart for biochemical analysis. Pancreatic tissues were obtained for analysis of glutathione peroxidase (GPx), glutathione s-transferase (GST), lipid peroxide levels (MDA) and histology analysis was examined for pancreas. Results indicated that treatment with simvastatin significantly enhanced levels of GPx and GST and decreased lipid peroxide levels induced by L-arginine compared to the vehicle. Moreover, histopathological analysis further confirmed that administration of simvastatin relatively prevented pancreatic acinar cell damage compared to those animals received L-arginine alone. These findings pointed out the protective role of simvastatin against acute pancreatitis induced by high doses of L-arginine.

Selected immuno-histochemical markers in curettage specimens and their correlation with final pathologic findings in endometrial cancer patients.

To assess the immuno-histochemical expression of various markers in, endometrial biopsies of patients with endometrial cancer, and to correlate their expression with the final pathologic findings. Sixty-two patients with primary endometrial cancer who underwent surgical treatment were included in this study. Immuno-histochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2, Her-2/neu and Ki-67 were assessed in curettage specimens, and review of the final pathology report from hysterectomy specimens was carried out. The expression of these markers in curettage was correlated with the final tumor characteristics obtained on hysterectomy specimens. Both ER and PR were significantly more expressed in endometrioid type (EC) than non- endometrioid type (NEC) (P value of 0.004 and 0.012). On the contrary, P53, Her-2 and Ki-67 showed higher positivity in NEC than EC (P value of 0.005, 0.025 and 0.002). Positive expression of ER and PR was significantly associated with low grade tumors and superficial myometrial invasion, whereas positive expression of Her-2 and Ki-67 was significantly associated with higher grade lesions, and deep myometrial invasion. Moreover, a statistically significant inverse relationship was observed between the positivity of P53, Her-2 and Ki-67 and the positivity of ER, PR. We found that determination of immuno-histochemical markers in curettage specimens might be helpful in predicting the final pathologic findings in patients with endometrial cancer. This might be helpful in planning the extensivity of the surgery.

Multi-drug resistance 1 genetic polymorphism and prediction of chemotherapy response in Hodgkin's Lymphoma.

BACKGROUND: The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen. METHODS: a total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism. RESULTS: these studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05). CONCLUSIONS: these results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.

An intelligent decision support system for quantitative assessment of gastric atrophy.

AIMS: To build an automated decision support system to assist pathologists in grading gastric atrophy according to the updated Sydney system. METHODS: A database of 143 biopsies was used to train and examine the proposed system. A panel of three experienced pathologists reached a consensus regarding the grading of the studied biopsies using the visual scale of the updated Sydney system. Digital imaging techniques were utilised to extract a set of discriminating morphological features that describe each atrophy grade sufficiently and uniquely. A probabilistic neural networks structure was used to build a grading system. To evaluate the performance of the proposed system, 66% of the biopsies (94 biopsy images) were used for training purposes and 34% (49 biopsy images) were used for testing and validation purposes. RESULTS: During the training phase, a 98.9% precision was achieved, whereas during testing, a precision of 95.9% was achieved. The overall precision achieved was 97.9%. CONCLUSIONS: A fully automated decision support system to grade gastric atrophy according to the updated Sydney system is proposed. The system utilises advanced image processing techniques and probabilistic neural networks in conducting the assessment. The proposed system eliminates inter- and intra-observer variations with high reproducibility.

Characteristics of gastrointestinal stromal tumors in a Middle Eastern population.

OBJECTIVE: To demonstrate the immunohistochemical and epidemiological characteristics of gastrointestinal stromal tumors (GIST) in a Middle Eastern population. METHODS: This is a retrospective analysis of all intra-abdominal mesenchymal tumors (excluding childhood embryonal rhabdomyosarcoma and small round blue cell tumors) collected from the archives of the Pathology Departments of King Hussein Cancer Center, Amman, and King Abdullah University Hospital, Irbid, Jordan between 2001 and 2008. The immunohistochemical profile of all cases was studied at King Hussein Cancer Center, Amman, Jordan, between January and August 2009. RESULTS: Gastrointestinal stromal tumors comprised 45% of the intra-abdominal mesenchymal tumors (42 out of 93 cases), with the most common site being the stomach (n=17, 40.5%). Twenty-seven GIST cases (64.3%) were classified as high risk, 4 (9.5%) as intermediate risk, 6 (14.3%) as low risk, and 2 (4.8%) as very low risk. Immunohistochemistry showed diffuse and strong positivity (+3) for CD117 in 85.7% of GIST cases, and for CD34 in 65% of cases. The high-risk tumors were more common in male patients (M:F=1.7:1), while the non-high risk tumors were more common in female patients. CONCLUSION: The immunohistochemical profile of GIST in Jordanian patients is similar to previously published data from other populations, with a slight male preponderance for high-risk GISTs.

Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78.

Here we report that paclitaxel induces variable degrees of apoptosis in human colorectal cancer cells. Paclitaxel induces multiple arms of the endoplasmic reticulum stress response, including upregulation of the 78-kDa glucose-regulatory protein (GRP78) and eukaryotic initiation factor alpha phosphorylation. Inhibition of the MEK/ERK pathway sensitized colorectal cancer cells to paclitaxel-induced apoptosis. A similar result was obtained by the inhibition of GRP78 using small interfering RNA molecules. Knockdown of MEK resulted in a significant downregulation of paclitaxel-induced upregulation of GRP78 indicating that activation of GRP78 is a downstream event of MEK/ERK pathway activation. These results indicate that GRP78 might be a novel mechanism underlying the resistance of colorectal cancer cells to microtubule-targeting drugs. A combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes.

Diaphragm disease of the jejunum.

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with the development of diaphragm disease. We report a 73-year-old male patient with this condition who had used NSAIDs for 2 years. He presented with general weakness, syncopal attacks, and a short history of melena. At laparotomy, multiple areas of constricted bowel were found in the resected proximal jejunum. Gross and microscopic examination confirmed diaphragm disease. The relevant literature is reviewed.