Zingerone Alleviate Toxicity Induced by Cisplatin or Gamma Radiation in Rats by Modulating Pro-Inflammatory Mediators

Background: Zingerone is one of the active components of ginger that possesses multiple biological activities and anti-inflammatory properties against either radiation effect or cisplatin toxicity. Purpose: to examine the protective effect of zingerone against gamma radiation (IR) or cisplatin-induced immunotoxicity. Material and Methods: 48 rats were divided into six groups as follows: (group-1); normal control group received distilled water; (group-2); rats received Zingerone orally at a dose of 25 mg/kg b.wt. Once / day for 14 consecutive days (Zing.). (group-3); Rats were given a single injection of Cisplatin at a dose of 7.5 mg/kg b.wt. intraperitoneally (Cispl.). (group-4); Rats exposed to a single dose of 6 Gy whole-body gamma irradiation using 137Cesium source in a Gamma cell 40 (Rad.). (group-5); rats received same dose of Zingerone then they were exposed to gamma radiation as in group 4 (Zing+Rad.). (group-6); rats received Zingerone followed by single injection of Cisplatin at the dose of 7.5 mg/kg b.wt. Intraperitoneally (Zing+Cisp.). Results: Exhibited a significant increase in expression of NF-κB, IL-10, caspase-3, and gene expression of TNF-α as well as oxidative stress biomarkers (MDA and NO) levels accompanied with a reduced level of SOD in either whole body-irradiated or cisplatin-received group. Conversely, pro-inflammatory cytokines levels were significantly decreased with an improvement of oxidative stress in groups that received zingerone. Conclusion: It could be concluded that zingerone exerts its antioxidative activity and immunomodulatory effects through inhibition of pro-inflammatory mediators induced by whole body-gamma irradiation or cisplatin administration at two time interval early and late stage of radiation exposure (after 2 h and one week).Therefore, further studies are required to elucidate the molecular signaling pathway concerning zingerone.

Karapandzic Flap for Functional & Cosmetic Reconstruction of Lower Lip Cancer with Review of Literature

The incidence and prevalence of lip and oral cavity cancer has increased over the last decade, worldwide and in India. It ranks at 1st position in males in india, all ages, in 2020. Lips are essential organ of the body which carries dynamic role in facial expression, speech, sensuality, deglutition. Resection of central, large, lower lip cancer creates a more than 2/3rd large defect. Covering of this defect with maintenance of oral competency is a difficult task for a treating surgeon. Number of techniques are described for covering of large lower lip defects. Out of these techniques, karapandzic flap is a successful, accepted, simple, easy to learn reconstructive procedure with good cosmetic results. It is a modification of Gillie’s fan flap and it involves unilateral or bilateral full-thickness circumoral advancement-rotation flaps. The feature which distinguishes it from other techniques is preservation of neuro-vascular integrity, symmetry and oral competency. We are reporting a case of an elderly gentleman with large, central, lower lip cancer who underwent oncological resection with reconstruction by karapandzic flap technique.

Nodular fasciitis: USP6-associated neoplasia through multiple pathways

Even though nodular fasciitis (NF) is benign and self-limited nature, the presentations of clinical, ultrasonographic, and pathological features have been described as mimicking sarcoma. Erickson-Johnson et al. suggested that ubiquitin-specific protease 6 (USP6) transcriptional upregulation may be the driving force behind the high proliferative activity and growth of NF. When the lesion showed the proliferative findings of the margin on both ultrasonography (US) and pathology, accompanied by clinically rapid growth, self-limited and/or regress course, NF could be strongly suggested as previously described. In this article, the author reviews the current knowledge of NF as USP6-associated neoplasia and also describes the therapeutic strategy in NF. In addition to the presentations of clinical, ulrtrasonographic, and pathological appearances of NF, the evaluation of percentage of USP6 break-apart FISH signals reflecting lifetime and mitotic counts in NF may be a potential procedure for accurate diagnosis in particularly young NF. It is putative that the inhibition of USP6-related genes might be the potential therapeutic strategies for the extremely rare malignant nodular fasciitis.

ETV6/RUNX1 fusion gene and its active role

Recent investigation successfully identified a pre leukemic ETV6/RUNX1-positive clone in the healthy twin of a patient diagnosed with ETV6/RUNXI-positive acute lymphoblastic leukemia (ALL) and also some studies with ETV6/RUNX1 knock in mice showed that the expression of the fusion gene is not sufficient for the invivo induction of ALL. Taken together, these data indicate that ETV6/RUNX1-positive leukemia is .generated through a multi-step mechanism, and that accumulation of additional genetic changes is necessary for the development of overt leukemia. Hence, to understand fully the genetic evolution of this disorder, identification of the complete spectrum of genetic changes that accompany the ETV6/RUNX1 fusion gene is necessary. Moreover, critical patho genetic insights may be gained from studying the correlation pattern of the different copy number changes.

Carcinoma en cuirasse associated to zosteriform metastasis from breast adenocarcinoma

We report an original case of carcinoma en cuirasse associated with zosteriform metastasis. A 40-year-old woman presented to our department with painful erythematous lesions. She had a history of invasive ductal carcinoma of the left breast. Numerous erythematous, papules and whitish vesicles were present over the right side of the chest in a dermatomal distribution with indurated coalescent plaques. Biopsy revealed metastatic carcinoma of breast origin. Breast mammography showed suspicious right nodule. Controlateral breast carcinoma with CM was diagnosed. CM show a wide range of clinical manifestations. Carcinoma en cuirasse, is a very rare form of metastatic cutaneous breast cancer. It is characterized by diffuse sclerodermatous induration of the skin. Zosteriform metastasis is also rarely seen. It may be distributed along dermatomeres in a variety of clinical patterns, including nodular, papulovesicular, or vesiculobullous. In our case, the zosteriform metastasis occurred in the contralateral site. It announced the developing of contralateral breast cancer.

CCNG1 oncogene: a novel biomarker for cancer therapy /gene therapy

Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor-targeted retrovector encoding a gene-edited dominant-negative CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, malignant peripheral nerve sheath tumor, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 (Cyclin G1-blocking) inhibitor therapy. Methods: CCNG1 RNA expression levels that were previously measured as part of whole genome molecular profiling of tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites were analyzed. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared in primary (N=103) vs. metastatic (N=367) skin cancers (i.e., melanoma). Statistical Analysis: To detect systematically differential expression of CCNG1 and Ki-67 expression between populations (e.g. tumor vs. normal), unpaired Student's t-tests were performed. Results: Enhanced CCNG1 RNA and Cyclin G1 protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Moreover, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors. Conclusions: Taken together with the emerging Cyclin G1 / Cdk / Myc / Mdm2 / p53 Axis governing Cancer Stem Cell Competence, this supportive data indicates: (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may actually be a stronger prognostic marker of stem cell competence, chemo-refractoriness, and EMT/metastasis than Ki-67. Phase 2 studies are planned to identify patients most likely to respond favorably to CCNG1 inhibitor therapy.

Association of Early Favipiravir Use with Reduced COVID-19 Fatality among Hospitalized Patients

Background: The antiviral agent favipiravir is an RNA-dependent RNA polymerase (RdRp) inhibitor. Materials and Methods: We examined patients with a clinical, laboratory, and radiological diagnosis of severe coronavirus disease 2019 (COVID-19) pneumonia. We investigated the effect of administering enteral favipiravir at a 2 × 1,600 mg loading dose and 2 × 600 mg maintenance dose for 5 days in addition to the standard COVID-19 treatment. Results: In total, 180 patients, who were hospitalized at the Istanbul Tuzla State Hospital and received favipiravir treatment between March 20, 2020 and May 30, 2020, were examined. Of these, 47 patients died. Thirty-three of the patients who died were aged over 65 years (70%), indicating that fatality was higher in elderly patients. Most of those who died had at least one comorbidity. Of the 101 patients who initiated favipiravir within ≤3 days of hospitalization, 17 died (17%). Of the 79 patients who initiated favipiravir after >3 days of hospitalization, 30 died (38%) (P = 0.002). Conclusion: We found that initiation of favipiravir within the first 72 h after the onset of disease symptoms reduced fatality in patients with COVID-19.

Outcome of Colorectal cancer in Geriatric Patient

Background: Older surgical patients remain at increased risk of adverse postoperative outcome when undergoing both elective and emergency surgery. The needs of the older surgical patient are often substantially different from those of younger patients. As a surgeons we have dilemmas in appropriately treating elderly patients. Specifically, those with cancer have been shown to receive inappropriate care, being either undertreated or overtreated based on their chronological age rather than their degree of frailty. Aim:To evaluate outcome of patients diagnosed with colorectal cancer in patients aged 80 years and over. Methods:Retrospective study of all patients 80 years and above managed with colorectal cancer at the Luton and Dunstable University Hospital UK from January 2015 through December 2019 Results: In the study period 278 patients were diagnosed with colorectal cancer, Male 143 Female 135 ratio 1:1.05. Age range from 80 to 101years. 54.31% patients underwent surgical intervention. 15.10% had complications after surgery. 36.69% patients deemed unsuitable for resection surgery were treated with best supportive care palliatively. 57.19% patients were in ASAIII, 24.10% ASAII and 12.23% ASAIV. 46.40% patients died during the study period. Conclusion:Age on its own would not be taken as for less aggressive therapy; Careful assessment of the patient taking into consideration comorbidities, functional status and patient wishes are essential in decision making and choosing appropriate management plan. Curative surgery for colorectal carcinoma in the geriatric patients are well tolerated. Management of comorbidities preceding surgery may impact postoperative outcome.

A successful ovarian cancer case

A lady discovered she had ovarian cancer in 2016 and was treated by CellSonic. The tumour remained big and had to be surgically removed after the cancer was stopped. Since then, cancer diagnostics have progressed and the electrical properties can now be easily detected allowing CellSonic to advance from stopping cancer in a patient to stopping cancer in a population. The patient is well and has approved this article.

Polypeptidic Taxol-Tropins: Targeting paclitaxel to the tumor microenvironment

Background and Rationale: Although PTX is widely used as a single chemotherapeutic agent and in various combination regimens, its clinical utility is hindered by acquired drug resistance and serious dose-limiting side effects that result from the ungoverned biodistribution of the taxane. Hypothesis: Conceptually, the precision, validity, and efficiency of paclitaxel delivery to tumor compartments might be substantially improved by “actively targeting” the exposed collagenous (XC-) proteins presented within the tumor microenvironment (TME)—XC-proteins physically exposed by the pathologic biochemical processes of tumor invasion, reactive stroma formation, and neo-angiogenesis. Objective: An adaptive bioengineering approach aims to apply pathotropic tumor-targeting functionality to paclitaxel (PTX), a powerful cytotoxic taxane which exhibits anti-tubulin / anti-mitotic / anti-cancer activities against a broad range of solid tumors. Materials and Methods: Synthetic peptide XC-targeting probes (< 40 aa) and polypeptide aptamers (40 to 53 aa), 85 - 99% purity, were prepared by 9-fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis, purified by high performance liquid chromatography (HPLC), and verified by mass spectrometry and amino acid analysis, and the XC-targeting probes were FITC-labeled. Analysis of fluorescence in XC-binding assays was visualized with an Ultra Bright Blue Light trans-illuminator equipped with an amber filter; photo-documentation was provided by a Leica V-Lux 1 digital camera; and comparative fluorescence was quantified using a Quantus benchtop fluorimeter (Promega). The tumor-targeting properties of Taxol-Tropins were tested in vitro by Taxol-aptamer binding assays and collagen-agarose binding assays and the bioactivities of PTX bound non-covalently toTaxol-Tropin aptamers were tested on XC-agarose beads. Further, the tumor targeting property of the Taxol-Tropin aptamers was tested in vivo in a murine model of metastatic cancer. Results: Here we report on the first actively targeted delivery of paclitaxel utilizing bifunctional polypeptide targeting onco-aptamers, called Taxol-Tropins, which: (i) bind PTX upon simple mixing with suitably high affinities and; (ii) bind exposed XC-proteins, thereby promoting enhanced partitioning and drug delivery into the TME. The bifunctional peptide sequence-optimized Taxol-Tropins bound tightly non-covalently to PTX and also exhibited high affinity and selectivity for XC-agarose beads in vitro. Importantly, the cytotoxic bioactivity of the Taxol-Tropin-bound-PTX molecule was well preserved in cellulo, as was demonstrated by cytocidal activity observed in MDA-MB-231 breast cancer cell cultures. Tumor-targeted PTX delivery by Taxol-Tropin onco-aptamers in vivo was modeled by subcutaneous xenografts of human pancreatic cancer in nude mice: where intense fluorescence of the PTX probe was observed in tumors of mice injected with the Taxol-Tropin-bound-PTX within minutes after intravenous injection, but not in untreated mice or mice treated with non-targeted PTX probe. Conclusions: These results demonstrate the feasibility of pro-actively targeting PTX, a clinically important small molecule, using Taxol-Tropins: synthetic polypeptide onco-aptamers, revealing optimized drug binding sequences and structural modifications pertinent to further clinical development of the tumor-targeting platform which may indeed shift the Therapeutic Index of PTX to one of greater clinical efficacy at lower drug doses.