Current Cancer Therapy Reviews - Volume 18, Issue 4, 2022

Erythrocyte could reach the tumor microenvironment after hemorrhage. Previous studies have proved that intratumor erythrocytes promote tumor cell proliferation and growth, while inducing an immunosuppressive state. In this viewpoint, it is propose that a metabolite-induced immunosuppressive function of red blood cells could be triggered in the tumor microenvironment. Specifically, the presence of erythrocytes in a microenvironment with low glucose and glutamine, high cholesterol, lactate and lysophosphatidic acid, and inducers of erythrocyte death, could result in immunosuppression.

Hepatocellular carcinoma (HCC) is the second malignancy worldwide. Dysregulation of various signaling pathways has been detected in HCC. Recent investigations have suggested a new approach for the prevention and treatment of HCC with herbal drugs. The anticancer effects of herbal drugs can be evaluated in animal models or HCC cell lines. Various molecular mechanisms and signaling pathways such as TGF-β, Wnt/β-catenin, SHH, Notch, Hippo, PI3K, and VEGF have been found to induce and promote carcinogenesis of HCC. Herbal drugs can target the signaling pathways in HCC and trigger apoptosis, suppress proliferation, and tumor growth. Molecularly targeted therapies using herbal drugs can be novel therapeutic strategies against HCC. This study provides the latest findings on using herbal medicine-derived compounds in the control of HCC.

Significant progress in anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated to generate more effective anti-cancer therapeutics. There have been many attempts to treat cancer. Based on diverse research, this review summarizes many bioactive substances obtained from nature that can fight against different types of malignancies with minimal harm. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment. Throughout the text, it was concluded that natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects, which are prominent with the conventional drugs used for the treatment of cancer.

Background: Worldwide, cancer patients are facing problems with life-and-death decisions due to the associated severe adverse and sometimes fatal effects of existing conventional treatments. Due to the severe adverse effects of existing therapies, effective cures are progressively explored for anticancer treatment. Mostly the conventional therapies are based upon nonspecific cellular destruction properties; therefore, a treatment approach is desired to reduce the toxic burden upon normal tissues. Among all alternative medicine systems, homeopathy is one of the most popular treatments for cancer patients globally due to its minimal side effects. Methods: In this present review, we have attempted to comprehend the literature reports on homeopathic medicine in cancer treatment. Results: Homeopathy has also proved its adjuvant approach to minimizing the symptomatic consequences of cancer. However, the insufficiency of evidence and lack of recurrence of the trials cause difficulty in drawing any conclusion about homeopathy as adjuvant therapy. Based upon the etiology, the genoprotective potential of homeopathic drugs was reviewed and found inconsequential evaluation and scanty literature. Conclusion: Hence, the present review gives a comprehensive summary of retrospective studies and suggests an integration of rational drug selection, standard protocols, and quantitative analysis for revealing the differential role and plausible application of homeopathy in better cancer management.

Oncolytic viruses replicate and spread in tumors at the same time, resulting in increased cytotoxicity and the reversal of tumor immune suppression. Among other viruses, recombinant adenoviruses replicated in tumor cells were clinically tested via intratumoral or systemic administration. Although oncolytic virus replication kills tumor cells on its own, it may also activate the immune system, which can aid in tumor control. Viruses can be modified to improve their selectivity and effectiveness. Adenovirus genomes can be easily designed to incorporate various tumor-targeting pathways and therapeutic transgenes to improve antitumor properties. Poor tumor targeting, intratumoral expansion, and virocentric immune responses are all linked to low efficacy. As a result, more effective oncolytic adenoviruses that can be used alone or in combination with chemotherapy or immunotherapy are needed. Oncolytic Adenovirus (OAds) has long been considered a potential biotherapeutic agent against various cancers due to its ability to replicate cancer cells while remaining dormant in healthy cells selectively. In recent years, several preclinical studies using genetic engineering technology have increased antitumor OAds in various cancers. Systemic OAds administration is hampered by poor targeting tropism to healthy tissues, low-level ad receptors on tumor cells, and pre-existing neutralizing antibodies. Various discoveries have been made to overcome these barriers, including stem cells, nanoparticles, polymer shielding, extracellular vesicles, hydrogels, and microparticles (MPs). These carriers may improve Oncolytic viruses’ therapeutic efficacy by improving transfection, circulatory survival, cellular interactions, specific targeting, and immune response. The structure and biology of adenoviruses, the different types of OAds, and the efficacy of different carriers in the systemic administration of OAds were all examined in this review.

Background: It has been shown that some drugs used as parenteral affect biochemical measurements. Anti-inflammatory and analgesic drugs may also have the potential to affect measurement methods. Objective: The aim of the study was to investigate the effects of seven different anti-inflammatory and analgesic pharmacological agents commonly used in wards and intensive care units on thyroglobulin, CA125, CA15-3, CA19-9, CEA, PSA and total HCG tests measured by immunoassay technique. Methods: The study was performed using hormone control material (BioRad Lyphocheck Immunoassay Plus Control) in the PETINIA immunoassay method (Siemens, Atellica, USA). 20 μL of tenoxicam, dexamethasone, methylprednisolone, paracetamol, diclofenac sodium, dexketoprofen, and metamizole sodium were added into 180 μL of the control solution, respectively. After vortexing the sample, it was incubated for 20 minutes at room temperature. Thyroglobulin, CA125, CA15- 3, CA19-9, CEA, total PSA and total HCG tests were studied from the control sample. The study was re-performed by adding 20 μL of distilled water. The measurements were repeated 3 times, and the mean values were recorded. Percentage deviation rates from the target value were calculated. Results: Metamizole sodium led to negative interference in the CA 19-9, total HCG, CA 125, CEA, total PSA and CA15-3 at a rate of -42.1%, -24.62%, -24.34%, -23.66%, -14.33%, and -13.91%, respectively. With the administration of metamizole sodium, the only positive interference was determined at a rate of 6.02% in thyroglobulin. Paracetamol-induced maximum deviation was calculated at the rate of -26.41% in CA 19-9. CA 19-9 deviated -12.22% from diclofenac sodium and - 22.41% from dexketoprofen. With methylprednisolone administration, positive interference was detected at a rate of 14.46% in thyroglobulin and negative interference at a rate of -12% in total PSA. The highest deviation due to dexketoprofen was seen in CA 19-9 at a rate of -22.41%. Conclusion: This study demonstrated the potential of anti-inflammatory, analgesic, and antipyretic agents to affect tumor marker measurements. Especially in the follow-up of cancer patients, antiinflammatory interference may increase the likelihood of malpractice by causing erroneous clinical evaluations.

Background: Despite the high efficacy rate of paclitaxel, physicians are compelled to discontinue the regimen due to its prevailing neurotoxicity and myelosuppressive effects, thus not achieving the desired clinical outcomes. The neurotoxicity studies of paclitaxel have been mostly performed on upper dose limits (>275mg/m²), and little information is available on lower doses. Since there is a lack of such studies on the Indian population, the medical professionals are unable to analyze at what cumulative dose does paclitaxel show maximum severity of peripheral neuropathy. Methods: This is a prospective observational study conducted for 1 year in patients undergoing paclitaxel therapy. These patients were evaluated for the incidence and severity of paclitaxel-induced peripheral neuropathy during the first 6 cycles using the QLQ-CIPN questionnaire. We also identified the cumulative dose at which most patients developed peripheral neuropathy and each patient’s quality of life using EORTC QLQ C30. Results: Out of 85 patients, 76 developed peripheral neuropathy during the first 6 cycles. It was observed that the severity of peripheral neuropathy increased in each cycle of therapy. The overall quality of life of patients decreased with therapy, and at a cumulative dose of 525mg/m², most of the patients (40%) developed symptoms of peripheral neuropathy. Conclusion: The incidence and severity of peripheral neuropathy increased with each cycle, leading to a significant reduction in the quality of life of patients post 6 cycles. Moreover, a high cumulative dose may limit the paclitaxel therapy.

Background: Breast cancer is the most prevalent cancer in women worldwide, causing the greatest number of cancer-related deaths. This study aimed to evaluate the use of healthcare resources associated with female breast cancer in Spain, to analyze trends in hospitalization and death rates, and the related direct medical costs. Methods: A retrospective multicenter study analyzed records of hospital and ambulatory visits of women diagnosed with breast cancer in Spanish hospitals between 1st January 2005 and 31st December 2018. Results: In total, 353,080 admission files were reviewed, mainly inpatient hospital admissions, corresponding to 299,585 individual patients. The median patient age was 59 years, 12.7% of admissions registered the presence of metastatic tumors, and 15.7% registered unspecified secondary tumors. The mean in-hospital death rate was 3.0% for patients without a metastatic disease and 10.5% for patients with metastatic disease, decreasing significantly over the study period. The total ageadjusted hospitalization rate increased between 2005 and 2011 and decreased after 2012. The mean direct medical cost was 3824 per outpatient visit, 3995 per hospital admission up to 3 days and 5001 per hospital admission over 3 days. Admission costs increased in patients with metastatic disease and those deceased during hospitalization. Conclusion: This study supports previous findings regarding the relative increase in breast cancer incidence that could be attributed to the intensive screening and the reduction in the death rate. Mean direct medical cost in this study varied greatly with the length of stay, presence of metastatic tumors and disease fatality.

Background: In recent decades, the exposure to doxorubicin (DOX) has elevated due to the increment in the incidence of cancer, especially among the young population, which, despite the desired restorative impacts, threatened the quality of life of survivors, particularly concerning their reproductive ability. Objectives: Although previous studies have shown the effectiveness of quercetin (QCT) and vitamin E (Vit. E), two major dietary antioxidants with favorable attributes regarding the female reproductive system, on doxorubicin-induced insulting to the ovary and, uterus, the mechanisms involved in responding to stress and inflammation have not been elucidated. Hence, this study sought to evaluate the preventive effects of these two antioxidants on doxorubicin-induced disruption of ovarian and uterine stress and inflammation. Methods: The study involved 48 female rats that were equally allocated into 6 groups; control (CON), QCT (20mg/Kg), Vit. E (200mg/Kg), DOX (accumulative 15mg/Kg), DOX+QCT, and DOX+Vit.E. Upon 21 days treatment, the activity of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione-dependent system, Total Antioxidant Capacity (TAC), Malondialdehyde (MDA), Nitric Oxide (NO), and Tumor Necrosis Factor-alpha (TNF-α) in the reproductive tissues and serum were evaluated. Results: Findings demonstrated that the levels of CAT, SOD, Glutathione Peroxidase (GPx), and TAC were alleviated by the studied antioxidants in both tissues (p-value<0.05). Furthermore, both supplements revealed ameliorative effects on DOX-induced alterations in NO, MDA (pvalue< 0.001), and TNF-α levels. Conclusion: Taking together, the present findings suggested the promising alleviative properties of QCT and Vit. E via modulating stress- and inflammation-responsive mechanisms against DOXinduced female reproductive toxicity.

Introduction: The pharmacogenetics of anticancer drugs is of paramount importance in minimizing their side effects and increasing their efficacy. When applied to capecitabine, the result is that variation in patient responses has been largely linked to different genetic polymorphisms of dihydropyrimidine dehydrogenase (DPD), which explained in many cases, the onset of toxicity of this medication in patients. Failure of this enzyme is known to be responsible for a high incidence of serious or fatal side effects. In this study conducted on Moroccan patients under treatment with capecitabine at usual doses at the Fez University Hospital, the first in Africa and Morocco, we are looking for the presence of four variants of the DPD gene (DPYD): T486A on exon 5 (rs666523971), c.1679T> G (p.I560S; rs55886062; allele DPYD * 13) on exon 13, c.1905 + 1G> A (IVS14 + 1G> A; rs3918290; allele DPYD * 2A) on the splice site near exon 14 and the c.2846A> T mutation (p.D949V; rs67376798) on exon 22. We will therefore seek to establish the cause-and-effect relationship between this toxicity and the presence of these variants in his patients, which will allow us to avoid the dangerous prescription of capecitabine in patients carrying these polymorphisms. Methods: This prospective study is carried out at the Laboratory of Medical Genetics of the CHU Hassan II Fez and spread over a period of 3 years. Patient recruitment was carried out by the oncology department of CHU Hassan II-Fès. All recruited patients are treated with capecitabine. A total of 64 patients were tested. Blood samples (5 ml) were obtained from each one of them after their consent, and DNA was extracted. The study of these four polymorphisms was carried out by PCR sequencing. Results and Discussion: We have studied 64 patients taking capecitabine. Their median age was 50, and the mean age was 50 and 79, with extremes of 25 and 78 years. The sex ratio F / M was 0,60. Different levels of toxicity have been developed in patients ranging from simple vomiting to IVdegree hand and foot syndrome and second-degree neuropathy involving total discontinuation of treatment. These mutations were not found in the patients. Thus it would be interesting to enlarge the sample size, look for these polymorphisms and others on other exons of the DPYD gene, and try to understand the cause of this increased incidence of capecitabine toxicity in the Moroccan population. Conclusion: Capecitabine-based chemotherapy caused adverse effects with varying levels in its patients. The SNPs on the DPYD gene sought were not found in this Moroccan sample. It is desirable to screen more patients and to search for other SNPs to understand the toxicity of capecitabine in relation to the DPYD gene. This will make it possible to adjust the dosage of this drug, increase its effectiveness and minimize its toxicity.

Background: Colorectal cancer (CC) is common cancer in humans and one of the major causes of cancer death worldwide. Recently, several therapeutic methods of CC and other malignancies have been developed, but drug resistance is an important problem in cancer treatment. Therefore, identifying and providing novel chemotherapeutic agents is important for treating malignancies. Objective: In the present study, we investigated the anti-cancer activity of Cuminum cyminum extraction using layered double hydroxide (LDH) nanosheets on the SW480 CC cell line. Methods: The anti-cancer activity of C. cyminum extraction and LDH nanosheets were investigated on the SW480 CC cell line by MTT assay. The mRNA expression of apoptosis-related genes (BAX and BCL2) was investigated by the Real-Time PCR method. Results: Our results revealed that extraction of C. cyminum significantly decreased proliferation and viability of SW480 CC cell line in a concentration-time-dependent manner. However, the antiproliferation effects of C. cyminum extraction by co-administration of LDH nanosheets were significantly more than its monotherapy. Moreover, the expression of BAX and BCL2 genes in the treated SW480 cells was significantly upregulated and downregulated, respectively. Conclusion: The present study generally revealed significant anti-cancer effects of C. cyminum extraction and LDH nanosheets combination on SW480 CC cells, which may be due to apoptosis induction.

Background: Cervical cancer is the second most common cancer found in pregnant women at a young age. Neoadjuvant with carboplatin and paclitaxel is often given to patients with cervical cancer, but the experience of administration during pregnancy is very limited. Case: A 22-year-old woman was diagnosed with stage IIA2 cervical cancer at 26 weeks gestation. The patient received three medications, including neoadjuvant chemotherapy, carboplatin, and paclitaxel, in three cycles with three weeks intervals at 27 weeks gestation. The patient underwent pregnancy termination with emergency cesarean delivery at 36 weeks of gestation and continued with a hysterectomy radical for 60 days, after which the patient received a chemoradiation adjuvant. Mother and baby were found healthy at one year after the diagnosis. Conclusion: NACT inhibited progression of the disease and allowed fetal maturity in locally advanced cervical cancer patient at a young age, followed by radical hysterectomy 60 weeks after cesarean section. The combination of carboplatin and paclitaxel seemed feasible and relatively safe for both the mother and the baby.