Nephrotic syndrome induced by cetuximab in a patient with metastatic colorectal cancer

Introduction Cetuximab, an anti-EGFR monoclonal antibody, often cause skin toxicity, most commonly acneiform rash. We present a rare case of glomerulonephritis associated with cetuximab therapy. Case Report A 58-year-old male patient recently completed cetuximab-based chemotherapy for metastatic colorectal adenocarcinoma. He presented with acute renal failure, anasarca edema and nephrotic proteinuria. The amount of protein in the 24-h urine test was over 15.6 grams. Management & Outcome The patient showed a dramatic improvement in renal function shortly after terminated of cetuximab therapy without immunosuppressive therapy. Discussion Therefore, drugs targeting epidermal growth factor receptor (EGFR) monoclonal antibody were thought to trigger nephrotic syndrome by causing glomerular damage. As a result, physicians using EGFR monoclonal inhibitors should be very careful about renal functions and proteinuria in patients.

Yolk Sac Tumor in a Recurrence of Colonic Adenocarcinoma With Shared Mutations in APC and TP53 Genes: A Case Report

Only four cases of colorectal adenocarcinoma with a yolk sac tumor (YST) component have been reported in the English literature. No genetic investigation has been performed in these cases. We report a case of colorectal adenocarcinoma in which the recurrent tumor had a YST component. A 49-year-old woman presented with a pelvic tumor three years after endoscopic mucosal resection of sigmoid colon adenocarcinoma. The pelvic tumor consisted of an undifferentiated carcinoma component and a YST component. The serum alpha-fetoprotein level was elevated to 42 ng/mL. Treatment as conventional colorectal carcinoma produced some anticancer effects, but the patient died 14 months after the recurrence and 49 months after the EMR. With the help of the next-generation sequencing results of the recurrent tumor, APC c.835 − 8A > G and TP53 c.524G > A (p.R175H) mutations were identified by direct sequencing in both the primary and the recurrent tumors, confirming the relationship between the two metachronous tumors.

5-Fluorouracil Neurotoxicity in the Absence of Dihydropyrimidine Dehydrogenase Deficiency Case Report

5 fluorouracil (5-FU)-related neurotoxicity is a rare and severe complication of 5-FU administration. Dihydropyrimidine dehydrogenase (DPD) deficiency is associated with an increased risk of serious adverse reactions due to its role in 5-FU metabolism. We report a case of acute reversible neurotoxicity with global areas of diffusion restriction in a patient with colorectal adenocarcinoma being treated with leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) without DPD deficiency following uridine triacetate administration.

Phytochemical Analysis and In Vitro Cytotoxic Activity against Colorectal Adenocarcinoma Cells of Hippophae rhamnodies L., Cymbopogon citratus (D.C.) Stapf, and Ocimum basilicum L. Essential Oils

Colorectal carcinoma (CRC) is one of the most frequently diagnosed cancer types with current deficient and aggressive treatment options, but various studied alternative therapies are able to efficiently contribute to its management. Essential oils (EOs) contain valuable compounds, with antibacterial, anti-inflammatory, and anticancer properties, which might serve as effective solutions in CRC prophylaxis or treatment. The aim of the present work was to evaluate the phytochemical composition and in vitro biological activity of essential oils derived from Hippophae rhamnoides (Hr_EO), Cymbopogon citratus (Cc_EO), and Ocimum basilicum (Ob_EO) species on HT-29 and Caco-2 human colorectal adenocarcinoma cell lines. The main compounds identified by GC-MS analysis were estragole (Hr_EO, Ob_EO), alpha- and beta-citral (Cc_EO). All tested EOs exerted a dose-dependent cytotoxicity on both cell lines by reducing the cell viability, especially in the case of Cc_EO, where at 75 µg/mL the viability percentages reached the values of 62.69% (Caco-2) and 64.09% (HT-29), respectively. The nuclear morphology evaluation highlighted significant dysmorphologies on both lines after their treatment with EOs at 75 µg/mL.

Prevalence of Colorectal Carcinoma With Respect to Age and Gender

Aim: Prevalence of colorectal carcinoma with respect to age and gender Study design: Observational / cross sectional study. Place and duration of study: This study was conducted at the Department of Pathology and Surgery, Post Graduate Medical Institute Lahore and Jinnah Medical College Peshawar from July, 2013 to February, 2015 Methodology: Surgical specimens of 60 histopathologically diagnosed cases of colorectal adenocarcinoma were included in this study. Age and sex were evaluated in CRC. Results: The mean±sd of age was 54.4±19.7 yrs. Out of 60 cases, 6 (10%) were between 16-29 yrs, 9 (15%) cases were between 30-49 yrs, 34 cases (56.7%) were of 50-69 yrs and 11 cases (18.33%) were of 70 yrs. Out of sixty cases, males were 33 (55%) and females were 27(45%). Conclusion: There are 34 out of 60(56.7%) patients were 50-69 years and 33 out of 60 (55%) cases were males i.e. males dominance. Keywords: Colorectal adenocarcinoma, immunohistochemistry, gender

The Expression and Activity of Rhodanese, 3-Mercaptopyruvate Sulfurtransferase, Cystathionine γ-Lyase in the Most Frequently Chosen Cellular Research Models

This paper provides information concerning the activity and expression levels of three sulfurtransferases (STRs): rhodanese (TST, EC: 2.8.1.1), 3-mercaptopyruvate sulfurtransferase (MPST, EC: 2.8.1.2) and cystathionine γ-lyase (CTH, EC: 4.4.1.1) in various cell lines. Since very limited data are available in the scientific literature on this subject, the available data are included in this paper. These shortages often force the researchers to carry out their own screening tests that allow them to choose an appropriate model for their further studies. This work supplements the existing deficiencies in this area and presents the activity and expression of STRs in the eight most frequently chosen cell lines: the mouse mammary gland cell line (NMuNG, ATCC: CRL-1636), mouse mammary gland tumor (4T1, ATCC: CRL-2539), mouse fibroblast (MEF, ATCC: SCRC-1008), mouse melanoma (B16-F1, ATCC: CRL-6323), human colorectal adenocarcinoma (Caco-2, ATCC: HTB-37), human embryonic kidney (HEK-293, ATCC: CRL-1573), human osteosarcoma (MG-63, ATCC: CRL-1427) and rat myocardium (H9c2, ATCC: CRL-1446). Changes in STRs activity are directly related to the bioavailability of cysteine and the sulfane sulfur level, and thus the present authors also measured these parameters, as well as the level of glutathione (its reduced (GSH) and oxidized (GSSG) form) and the [GSH]/[GSSG] ratio that determines the antioxidant capacity of the cells. STRs demonstrate diverse functionality and clinical relevance; therefore, we also performed an analysis of genetic variation of STRs genes that revealed a large number of polymorphisms. Although STRs still provide challenges in several fields, responding to them could not only improve the understanding of various diseases, but may also provide a way to treat them.

Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

Clinical significance of mucinous component in colorectal adenocarcinoma: a propensity score-matched study

Background This study aims to investigate the clinical significance and prognostic value of mucinous component (MC) in colorectal adenocarcinoma (AC). Methods Patients with colorectal AC and AC with MC (ACMC) (1–100%) underwent surgical resection between January 2007 and February 2018 were retrospectively reviewed. Propensity score matching (PSM) was performed according to a 1:1 ratio. Receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off value of MC ratio for prognostic prediction. The clinicopathological features and 3-year overall survival (OS) of AC patients, mucinous adenocarcinoma (MAC) (MC > 50%) patients, and ACMC (1–50%) patients were compared before and after matching. Multivariable analysis was used for analyzing independent risk factors related to prognosis. Results A total of 532 patients were enrolled in this study. Patients with AC, MAC, and ACMC (1–50%) exhibited different clinicopathological features. However, their 3-year OS rates were similar (82.00% vs. 74.11% vs. 81.48%, P = 0.38). After matching, ROC curve determined 70% as the optimal cut-off value. And patients with ACMC > 70% had a much poorer 3-year OS compared with ACMC (1–70%) patients and AC patients (47.37% vs. 86.15% vs. 79.76%, P < 0.001). In addition, ACMC > 70% was revealed as a risk factor for poor survival in univariate analysis (HR = 1.643, 95%CI = 1.025–2.635, P = 0.039), though not an independent risk factor in multivariable analysis (HR = 1.550, 95%CI = 0.958–2.507, P = 0.074). Conclusions MAC is usually diagnosed at an advanced stage. MAC has a similar survival with AC and ACMC (1–50%) patients before and after matching. Patients with ACMC > 70% exhibited a much poorer OS, and should be given more clinical attention.