Cancer Science & Therapy

Purpose: Disseminated tumor cells (DTCs) are critically involved in tumor relapse and survival in several invasive tumors. We previously showed that the ATP-binding cassette (ABC) transporter, ABCB5, is a chemoresistance mediator expressed on specific cell subsets in colorectal cancer (CRC) and other malignancies. This study evaluated the molecular signature expression and its clinical relevance of DTCs in bone marrow from patients with colon cancer.

Methods: This study included 49 consecutive patients (UICC stage I-IV) that underwent curatively intended or palliative surgery for CRC. We analyzed cells from bone marrow aspirates obtained before surgery and derived from patients that had completed minimally a 5-year follow-up. The gene expression of ABCB5 in comparison to CD133 (molecule for identifying cancer initiating cells), Lgr5 (an intestinal stem cell marker) as well as Cytokeratin (CK) 20 (terminally differentiated tumor cells of epithelial origin) in these cells was evaluated.

Results: Bone marrow analysis showed differential expression between the analyzed genes. ABCB5 and Lgr5 and to lesser extent CD133 and CK20 genes were significantly expressed in the analyzed cells from bone marrow aspirates while only ABCB5 and Lgr5 were significantly negative associated with tumor progress and overall survival.

Conclusion: Overexpression of ABCB5 and Lgr5 in bone marrow negatively influenced patient survival pointing to a specific chemo resistant and pluripotent cell subgroup of DTCs in the bone marrow. ABCB5 like Lgr5 positive cells seem to be involved in limited tumor related patient survival, suggesting that ABCB5- and Lgr5-positive cells may be relevant for specific clinical intervention strategies.

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction rates were numerically simulated with MATLAB. Here, our work shows that a robust immune response can be generated if the immune system recognizes epitopes that are between 8 to 11 amino acids long. We show through mathematical modeling of how synthetic tumor vaccines can be utilized to mitigate a developing cancer.

Background: Colorectal carcinoma (CRC) is a burden problem in a developing country like Egypt since patients are usually admitted in late stage with bad prognosis and short overall survival. Because of genetic predisposition of CRC and introduction of advanced molecular techniques, efforts are directed to screen for potential pathogenic or disease-causing variants in CRC patients

Methods: DNA was isolated from formalin fixed paraffin embedded tissue sections collected from 24 CRC confirmed diagnosed patients. TruSight CRC panel (Illumina) was used for detection of different variants in 15 genes. The generated reads were obtained from Illumina Miseq were clustered into single nucleotide polymorphism (SNPs) and small insertions/deletions (Indels). Further pathogenic variants with somatic and germline mutations were identified according to the recommended criteria. Some CRC patients were subjected to anti-EGFR target therapy.

Results: Most of the variants were detected in TP53 gene 140 variants (65%); 105 short deletions none of them was pathogenic, 29 missense mutations and 6 SNPs at splicing sites. Next, ERBB2 has got 17 variants (8.8%) (missense and splicing), 8 of them were damaging disease causing variants. Besides, 16 pathogenic variants were identified in 12 patients (6 in TP53 and 7 in KRAS). Some pathogenic variants were not reported before in CRC e.g. TP53 C>A, rs121912654, Val157Phe. Additionally, patients carried different KRAS wild mutations showed variable response to anti-EGFR target therapy.

Conclusion: The most affected pathway in CRC was TP53 pathway followed by ERBB2, NRAS, KRAS and PIK3CA genes. Variable response to target therapy suggested dependence on the type of pathogenic variant identified, also a possible role of ERBB2 which had a significant variant frequency.

The safety of anticancer dosing has become a serious concern due to high incidence of life-threatening toxicity signs. More so, dogs are used as models of research for human cancers. In view of these a uniform body surface area (BSA) formula has been derived for human and dog with a view to having low, safe, effective therapeutic doses of anticancers. The derived formula (BSA=BW0.528 × H0.528 × K) was used to calculate BSAs of greyhound, toy, companion, terrier, hunting and working dogs and yielded low effective therapeutic doses of dacarbazine, asparaginase, streptozotocin, dactinomycin, epirubicine and prednisolone. Hunting and working dogs have high body weight, BMI and BSAs similar to that of human and may be prone to obesity and obesity associated diseases. Whereas BSAs and doses of anticancer agents of light and relatively tall dogs are relatively higher in comparison with that of short and light dogs. Greyhounds have higher BSA in comparison with toys, companions and terriers. Working breeds of dog such as Treeing Walker Coon haired (65.0 kg), Great Swiss mountain dog (59.0 kg), longhaired St. Bernard (55.0 kg), French Mastiff (50.0 kg) and female Komondor (59.0 kg) have same BSA values with humans weighing 51.3, 46.7, 44.8, 44.0 and 43.0 kg, respectively. Calculated common exponent (0.528) for body weight and height may be the common relationship between basal metabolism of dog and human.

Breast cancer (BC) is considered as a major health problem in Sudan, being the most frequent hospital treated malignancy and the commonest cancer affecting Sudanese females (34%). Proteomics provides tools that investigate the precise molecular defect(s) in breast cancer tissue. Moreover, it plays a growingly important role in tumor markers discovery. In this study, a proteomic assay (2D-PAGE) was used to investigate the protein profiles of a panel of 12 Sudanese breast malignant tissues and 12 matched controls. Protein spots of interest were excised manually, and in-gel digested using trypsin. Proteins were identified using mass spectrometry (MALDITOF). Mascot program was used to search protein databases for matching peptides from known proteins. The overall profile was relatively similar, the preliminary results identified three proteins to be differentially expressed, suggesting that they may perform a role in breast neoplasia. Although the number of samples investigated in this study is comparatively small, to allow authoritative conclusions, the study provided three proteins that might be potential tumor markers in Sudanese breast cancer patients requiring further investigations and validation.

Objective: Borderline Ovarian Tumors (BOTs) have a good prognosis; however, a few BOT patients experience the relapse of disease, either borderline or malignant. The aims of this study were to analyze the risk factors of relapse.

Methods: This is a retrospective study of 31 patients with confirmed BOTs treated in the Salah Azaiez Oncologic institute between 2005 and 2015.

Results: 31 cases were identified; median age was 43 years. Most of the patients 27 (87%) demonstrated stage IA. 8 patients had laparoscopic surgery and they were all treated conservatively. Between 23 patients, which had laparotomy, only two cases underwent conservative surgery and the remaining patients had radical surgery. Five patients had recurrences (16.13%). The relapse was occurred meanly 62.38 months after the primary surgery. Among the 5 recurrent cases, one cancerous transformation and 4 borderline recurrences were detected. 3 recurrences of 8 Laparoscopic surgery group and 2 recurrent cases of 23 laparotomic surgery groups were observed but the statistic result of the relation between laparoscopic approach and higher recurrence rate was not significant (P=0.093). 3 recurrences of 10 conservative surgery group and 2 recurrent cases of 21 radical surgery groups were observed. However, it did not show significant difference (P=0.175). Mean age of disease-recurrence group was 42.8 years whereas the one of non-recurrent group was 46.5 years (P=0.65), age was not risk factor of disease recurrence.

Conclusion: Even if age, conservative treatment and laparoscopic technique does not reach the statistic significance as a risk factors for recurrence, we can have a definite conclusion. It is necessary to perform more randomized controlled trials to confirm such an assumption.

Primary signet-ring cell carcinoma of cervix is extremely rare in the literature. Usually Signet-Ring Cell Carcinomas (SRCCs) of the cervix are metastatic from a primary gastric, colonic, ovarian, or breast carcinoma. A 48-year-old woman was referred to our Department due to persistent abnormal vaginal bleeding during the last two months. Gynecologic examination revealed cervical tumor. Biopsy revealed a signet ring cell type of mucinous adenocarcinoma. Extensive systemic examination reveals liver metastases biopsies confirmed. The patient was treated with palliative chemotherapy. The prognosis of primary signet ring cell adenocarcinoma of the uterine cervix is still unclear because of the rare incidence of cases. In this report we reviewed the literature to identify the clinical, pathological and immunohistochemical features of this rare malignancy.