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肿瘤学转化研究杂志

体积 7, 问题 1 (2021)

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Modulation of the ROCK/Akt/eNOS pathway by simvastatin protects against 5-fluorouracil cardiotoxicity

Radwa Nasser Muhammad

5-Fluorouracil (5-FU) is a highly effective anticancer drug, widely incorporated in the management of different solid tumours, and is a cornerstone therapy in colorectal cancer. Its use is associated with a wide range of different toxicities, including several reports of fatal cardiotoxicity which was first reported four decades ago. Since then, only some efforts were done to understand the pathophysiology and molecular mechanisms associated with this type of toxicity, moreover; there is no effective preventive measure against this toxic effect. Until now, myocardial ischemia due to coronary vasospasm is the most accepted theory.

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Fine needle aspiration cytology of Jaw bone lesions emphasis on utility and pitfalls

Meenakshi Chowdhary

FNAC (Fine Needle Aspiration Cytology) of head and neck region was pioneered by Martin in the early 1930s. FNAC is a frequently used for diagnosis of abnormal masses. FNAC is minimally invasive first line investigation which can render an accurate preoperative diagnosis of intraosseous jaw lesions, especially the malignant ones in the enigmatic circle of clinic-radiological differentials. Although FNAC of intraosseous lesions is difficult to perform compared with soft tissue lesions, it still can be used for preoperative diagnosis in selected cases. Biopsy being gold standard of preoperative diagnosis would be cumbersome and traumatic when surgery is mainstay of treatment. Still, diagnostic evaluation of neoplastic and non-neoplastic lesions has increased dramatically when it comes to jaw lesions and surgery. For the diagnosis of lymph nodes, salivary glands, and thyroid and parathyroid gland diseases, FNAC have proven to be boon. It’s apt to mention that FNAC is a simple, rapid, and minimally invasive procedure in contrast to biopsy, its use in the diagnosis of odontogenic tumors including ameloblastomas. But role of FNAC in respect to typing of odontogenic tumors has not been explored much.

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Prospectus of Bacteriophages as natural antimicrobial agents for plant protection: A case study

Makari H K

Bacteriophages are the natural omnilytics and viruses of bacteria. Phage infects the bacteria more specifically, causes lytic or lysogenic activity in cells resulting in the death of the bacteria. Investigation on phages is a fast expanding area in agricultural biotechnology and in plant protection. Ralstonia solanacearum is a Gram negative bacteria causing devasting lethality in most of the solanaceous plants including potato and ginger, resulted in heavy economic losses world-wide. The chemical method of control of this bacterium is difficult because of its drug resistance. The use of alternative bactericidal agents is now prevalent over antibiotics and synthetic chemicals. This study was aimed to find natural antimicrobial agents specifically kill the bacterial population and results in reduction of pathogenicity.  R. solanacearum strains were isolated from wilting potato and ginger crops in Hassan district, Karnataka and were characterized by biochemical test and PCR based detection.

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Turn Around Time of Histopathological Surgical Biopsies and Delivery of Medical Services at the Jos University Teaching Hospital

Innocent Emmanuel

The developing world is arguably characterized by backwardness or rudimentary political, social, and economic systems of which the health system is not immune to resulting in worst health indices. Pathology services in these climes which are characterized by system delay in obtaining and processing biopsy samples and reporting the results, with consequent delay the starting of treatment. The broad objective of this research study is to determine the impact of service delivery on the turn-around time of histopathological surgical biopsies in Nigerian public Health sector with reference to the Jos University Teaching Hospital. Specifically, the objectives of this research study are to investigate the impact of reliability, assurance, tangibility, empathy and responsiveness on the turn-around time of the laboratory.

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Activities of raw and partially boiled quail (Coturnix Coturnix Japonica) eggs in increasing Megakaryocyte count among Aplasia-Induced mice

Hervae A. Ordoño, Raganit Marji Sim, Odiem Glenn Frey, Galacgac Mica Mae, Gumpad Grace Mae, Laza Abby Jane, Molina Trixie Anne, Orilla Kim Daryl and Pascual Glady Shiela

Megakaryocytes are among the largest cells in the body formed via multiple-staged megakaryopoiesis. These precursor cells release hemostasis-essential platelets into the circulation after undergoing thrombopoiesis. The significance of megakaryocytes and platelets is immediately apparent since a wide range of patients face morbidity and mortality from bleeding due to moderate to severe thrombocytopenia. In the tropics such as the Philippines, the mosquito borne viral disease dengue has become potentially deadly due to complications of plasma leaking, severe bleeding, and organ impairment. The bleeding mechanism for dengue remains poorly understood but the World Health Organization (WHO) specified thrombocytopenia with normal platelet function as a criterion. It has become potentially deadly due to its complications of plasma leakage, severe bleeding, and organ impairment. Quail eggs are packed with nutrients such as the B vitamins (B12, B9, and B3) which are vital for megakaryopoiesis. This study alleviates the negative effects of thrombocytopenia, the emerging cases of hemolytic disorders and dengue cases through the use of quail eggs. It has an impact on decreasing the need for blood transfusions in severe cases of dengue and hematopoietic disorders. It provides a less expensive and more accessible management for people who have problems in blood cell production and formation, especially megakaryocytes.

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Clinical applications of immunoglobulin expression in acute myeloid leukemia

C. Cameron Yin

It has been assumed that immunoglobulin (Ig) can only be produced by B-cells and plasma cells. Recently, we have reported that Ig can be expressed by other types of cells such as epithelial cancer cells. In this study, we assessed Ig expression in acute myeloid leukemia (AML). We found that Ig was expressed at a high frequency and level in AML cell lines and primary myeloblasts, but not in monocytes or neutrophils from healthy controls, by RT-PCR, immunohistochemistry and flow cytometry. We further assessed rearrangements of IgG VHDJH transcripts, and found that AML-IgG had restricted or biased V usage, and its gene rearrangements showed evidence of somatic hypermutation. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines, whereas anti-human IgK increased cell migration and chemotaxis. Furthermore, using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with different expression of Ig and different clinical outcomes. High-levels of Ig expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Our findings suggest that AML-Ig may play a role in leukemogenesis and AML progression, and it may serve as a useful molecular marker for prognostic stratification, monitoring minimal residual disease, and target therapy.

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Antiparkinsonian potential of cilostazol: insights into its neuroprotective effects

Shireen A. Hedya

Cilostazol, a 2-oxo-quinoline derivative, is a selective inhibitor of phosphodiesterase-3 that increases intracellular cAMP levels and activates protein kinase A. Cilostazol exhibited neuroprotection in focal cerebral ischemia in rats, which was attributed to its anti-apoptotic properties. Furthermore, it guarded against hypoperfusion-induced cognitive impairment resulting in protective activity in an animal model of vascular dementia. Interestingly, cilostazol proved to exert favourable effects against Alzheimer’s disease where it enhanced β-amyloid peptide degradation through autophagy modulation in N2a neuronal cells. Together, these findings further support the notion that cilostazol may possess neuroprotective effect and may show beneficial outcome in PD. The aim of this study is to explore the Neuroprotective effect of cilostazol in rotenone-induced PD model in rats. Parkinsonian rat pre-treated with cilostazol showed minimal neuronal vacuolation and minimal perivascular edema in the midbrain and striatum. Moreover, Pre-treatment of rats with cilostazol improved the motor deficits as verified by a remarkable surge in ambulation and rearing. This could be explained by the fact that cilostazol significantly raised striatal TH content as compared to the rotenone group. . In conclusion, cilostazol could be a promising candidate for PD treatment.

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Efficient method of cancer cells therapy repairing Quasi-stationary pathologic State of an organism into Stationary normal State of an organism

M.Ponizovskiy

The stable balance catabolic processes & anabolic processes induce cytoplasm’s basophilic chemical potential (μ) of stable basophilic coloration via staining
of cell forming the stabile Internal Energy of cell due to resonance waves of cellular capacitors operations according to first law of thermodynamics. Just cells’
stabile Internal Energy makes Stationary State as an organism and as well as cells of an organism in norm. The excessive shifts balance catabolic processes
& anabolic processes into abundance anabolic processes lead to transmutation into Quasi-stationary State both cancer cells and cancer tissues exhibiting
Warburg effect mechanism. Affecting by viral oncogenes, the excessive shifts balance catabolic processes & anabolic processes into huge anabolic processes
result in expression nuclear activity as center anabolic processes due also to operations of excessive ROS/H2O2/free radical produced in mitochondria that exert
irrepressible cancer proliferative processes. The method Cancer Therapy proposes combination “Prolonged medical starvation” with considerably decreased
dosage of cytotoxic drugs. The forced inflow of substances and energy in condition of prolonged medical starvation occurs from the organism’s depots both for
the organism metabolism and for the cancer cells metabolism. The exhausted organism’s depots in condition of prolonged medical starvation exerts mechanism
maintenance stabile Internal Energy of an organism (temperature 36,5ºC – 37,2ºC, by which all enzymes operate) that causes shift both an organism’s metabolism
and tumor metabolism into catabolic exergonic pathway violating anabolic endergonic processes in tumor metabolism. Thus inhibition of the abundance anabolic
endergonic processes, which characterize cancer metabolism, results in cancer cells depression. Thereby the treatment with considerably decreased dosages of
cytotoxic drugs in condition of depressed cancer cells’ metabolsim damage tumor metabolism and rearrange Warburg effect of cancer metabolism into Pasteur
effect of normal tissue metabolism, causing efficiently cancer therapy. The advantage of this method of cancer treatment is that this method of cancer disease
treatment does not intrude into the stability of Internal Medium and Internal Energy an organism and cells of an organism, does not violate defensive mechanisms
of an organism /the cells of immune and hormonal systems/ in comparison with targeting metabolic links of anabolic processes both in the organism’s cells
and in the tumor’s cells, causing damage of hormonal regulatory processes and protective immune processes in an organism by up-to-date chemotherapeutic
methods which use great dosage cytotoxic drugs. Therefore the efficient method cancer therapy using decreased dosage of cytotoxic drugs against depressed
cancer tumor does not lead to negative consequences how recurrence cancer disease after some medical remissions and resistance to cytotoxic drugs after
long anticancer therapy.

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Methodology for In Silico Modeling of p210BCR-ABL Oncoprotein Isoforms found in Chronic Myelogenous Leukemia

Nadeem Kizilbash, Jamal Alruwaili, Hassan M. Khachfe, Jaweria Ambreen and Shumaila Asif

Chronic Myelogenous Leukemia (CML) affects the hematopoietic stem cells of the bone marrow. It develops as a chromosomal abnormality due to the presence
of the Philadelphia chromosome carrying the BCR-ABL oncogene. This gene expresses two oncoprotein isoforms, b2a2 and b3a2, produced by the head-to-tail
fusion of p160BCR and p145ABL proteins. The two oncoproteins differ in amino sequence by a 25 residue insertion and a Glu903Asp substitution. In silico
modeling, using the PSIPRED server has provided the secondary structural elements of the two oncoprotein isoforms. This program normalizes the amino acid
sequences generated by PSIBLAST and then uses a neural network to produce the secondary structure. Chronic Myelogenous Leukemia (CML) develops when
a single, hematopoietic stem cell acquires a Philadelphia (Ph) chromosome carrying the BCR-ABL fusion oncogene which gives its progeny an advantage for
proliferation over normal RBCs and allows the Ph-positive clone gradually to displace normal RBCs during hematopoiesis. The abnormal Ph chromosome is
produced by the translocation between chromosomes. The major consequences of Philadelphia translocation is the fusion of the ABL gene on chromosome 9 with
the BCR gene on chromosome 22. The BCR-ABL fusion oncogene encodes new fusion proteins of 190, 210 and 230 kDa molecular weight. The p210BCR-ABL
isoforms have an increased level of tyrosine kinase activity, which is important for the development of the disease. The production of fusion proteins increases
the diversity of proteinprotein binding domains associated with tyrosine kinase activity.

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Information Needs of Breast Cancer Patients at Cancer Diseases Hospital, Lusaka, Zambia

Beauty Lilala Namushi, Marjorie Kabinga Makukula and Patricia Katowa Mukwato

Background: Breast Cancer is that the second commonest cancer worldwide and therefore the second commonest among Zambian women. Breast cancer
diagnosis being a stressful experience, causes psychological and emotional disruption which will be abated by meeting information needs of the affected
patients. In light of the escalating cases of carcinoma among the Zambian women, the study examined a special aspect of cancer management which is typically
neglected in most cases.
Aim: the most objective of the study was to assess information needs of carcinoma patients at the Cancer Diseases Hospital in Lusaka, Zambia employing a
modified structured interview schedule adopted from the Toronto Information Needs Questionnaire-Breast Cancer (TINQ-BC).
Methods: A descriptive cross-sectional design was used to elicit the information needs of breast cancer patients. One hundred and ten (97% response rate)
participants were selected using simple random sampling method and data was collected using a modified structured interview schedule adopted from the
Toronto Information Needs Questionnaire-Breast Cancer (TINQ-BC). Stata 10.0 (StataCorp, 2008) was employed for all quantitative data analysis and graphical
presentation of data.
Results: The overall score for information needs was obtained by adding the scores across all the five information needs categories which were further divided
into three categories namely: low important scores, of but 50%, moderately important many 50% - 70% and highly important scores ranged above 70% of the
200 total scores. Out of the 110 participants recruited, 88 (80%) indicated that the information across the five categories was moderately important. Logistic
regression of information needs and posited determinants revealed that anxiety levels; education level; presence of co-morbidity; and being on treatment were
significant determinants of patients’ informational needs (Effect’s p ≤ 0.05).
Conclusion: The findings of this study support the idea that breast cancer patients are seeking more information on their illness; hence information provision is
one of the most important factors for providing top quality cancer care across the entire cancer continuum. Therefore, appreciating the information needs of breast
cancer patients is substantial in improving care.

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Local and systemic inflammatory markers as prognostic and predictive markers in locally advanced triple negative breast cancer

Lamiss Mohamed Sad, Ayman Elsaka, Yomna Zamzam and Walid Ahmed Almorsy

Introduction: Local inflammatory markers have been defined as prognostic and predictive markers in triple negative markers as proved by many studies. The
prognostic and predictive value of systemic inflammatory markers such as neutrophil lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) remain to
be elucidated.
Aim of study: To evaluate pathological complete response (PCR) to neoadjuvant chemotherapy in locally advanced cancer breast in relation to tumor infiltrating
lymphocytes(TILs), neutrophil lymphocyte ratio and lymphocyte monocyte ratio as well as overall survival and disease free survival. Patients and methods: In
Tanta university Hospital, oncology department form January 2012 to December 2013, 67 patients with locally advanced TNBC stage IIB, IIIB 0r IIIC using TNM
8th edition. All patients received neoadjuvant chemotherapy in the form of dose dense AC followed by paclitaxel (adriamycin and cyclophosphamide 60 mgm/
m2 and 600 mgm/m2 respectively the cycle is repeated every 2 weeks for 4 cycles followed by paclitaxel 175mgm/m2 every 2 weeks for 4 cycles). All cycles with
G-CSF support. Pretreatment TILs, NLR and LMR were evaluated with PCR and as prognostic factor of survival. Results: Low NLR has been detected in 74.6%
of cases and has been associated with high TILs and this was statistically significant (p value=0.03). High LMR was observed in 80.6% of cases and correlated
significantly with TILs (p value=0.003). Pathological CR was found to be associated with high TILs, low NLR and high LMR. In our study we evaluated the pre
neoadjuvant systemic and local inflammatory markers as prognostic marker we found that in multivariate analysis, the lymphocyte monocyte ratio maintained
their statistical significance with overall survival. While tumor infiltrating lymphocyte maintained their statistical significance as prognostic factors with overall
survival and disease free survival. Conclusion: Systemic inflammatory markers can be used as marker of pathological complete response in locally advanced
triple negative breast6 cancer with neoadjuvant chemothe.

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Method proposed to prevent early (and maybe late) relapses in breast and other cancers

Michael Retsky

My colleagues and I have been studying a bimodal relapse pattern in breast cancer. This project started in 1993 when data from Italy and UK showed an
unexpected bimodal relapse pattern in breast cancer. It seemed that 50 to 80% of all relapses in patients treated only with surgery occurred in an early wave
of relapses in the first three years post-surgery. We have proposed a reasonable explanation over the years. It appears that the surgery to remove a primary
tumor causes systemic inflammation for a week. During that time, dormant single malignant cells and avascular deposits escape from dormancy and appear as
relapses within three years. The multi-national authors of these reports include medical oncologists, surgeons, anesthesiologists, physicists and other scientists
from several fields. A potential solution seems to exist based on our analysis, data, and retrospective studies. That therapy is the common inexpensive analgesic
ketorolac administered as iv at the time of surgery and perhaps as oral drug for a few days after surgery. We edited a book in 2017 that was published by
Springer-Nature (1) and a number of papers including one recently published (2). Other reports support this and suggest mechanisms (3-5). We now show data
that predicts this is a process that applies to many solid and other cancers. Based on data from lung cancer, inflammation level on the first day post-surgery
predicts outcome. We propose that this disruptive innovation will result in a paradigm shift in oncology. In a recent development we are now working on a method
to prevent late relapses as well. This would suggest that persons who are at risk of late relapse and going to have planned surgery for health or cosmetic reasons
should have perioperative ketorolac just as if the surgery was for cancer.

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Enhanced Recovery after Surgery (ERAS) pathways for patients with bone cancer who will undergo primary hip or knee arthroplasty, using large endoprosthesis

Maria Bourazani

Orthopedic prosthesis is widely used to restore joint function, relieve pain and improve the patient’s quality of life. Endoprosthesis are used in reconstructive
orthopedic surgery of large joints and in orthopedic surgical oncology after tumor resection (bone cancer). Enhanced Recovery after Surgery pathways (ERAS)
are applied to oncology patients undergoing primary THA or TKA; and through evidenced practices are used by the multidisciplinary team, with the aim of
reducing the length of stay (LOS) in hospital. ERAS pathways have been reported to reduce postoperative stress, to promote fast recovery, without increasing
complications or re-admissions. At the same time, ERAS pathways have been reported to increase patient satisfaction and surgical outcomes and reduce
hospital costs.
Aim: Implementing ERAS pathways for oncology patients with bone cancer who will undergo primary hip or knee arthroplasty, using large endoprosthesis.
Methods: Review in databases: PubMed, Elsevier, Cochrane and Google Scholar using keywords.
Conclusion: A lot of studies have shown that ERAS pathways are associated with reduced LOS in hospital, decreased complications, lower perioperative
stress levels, and better surgical outcomes, at lower in-hospital cost. ERAS pathways are involving the surgeon, the anesthesiologist, the perioperative nurse,
the physiotherapist, and when is needed the psychologist and the nutritionist as a multidisciplinary team. ERAS pathways include various techniques in three
phases, preoperative, intraoperative and postoperative. However, anesthesia plays a key-role as it affects immediate recovery, patient satisfaction, postoperative
complications such as delirium and nausea-vomiting (PONV), and in some cases with serious results.

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