Lung cancer vaccination from concept to reality: A critical review of clinical trials and latest advances.

Lung cancer is a highly lethal malignancy that poses a significant burden on public health worldwide. There have been numerous therapeutic approaches, among which cancer vaccines have emerged as a promising approach to harnessing the patient's immune system to induce long-lasting anti-tumor immunity. The current study aims to provide an overview of cancer vaccination in the context of lung cancer to establish a clearer landscape for lung cancer treatment. To provide a comprehensive review, we not only gathered the published studies of lung cancer vaccination and discussed their effectiveness and safety profile but also analyzed all the relevant clinical trials registered on www.clinicaltrials.gov until March 2024. We demonstrated all utilized vaccine platforms along with having a glance at novel technologies such as mRNA vaccines. The present review discussed the challenges and shortcomings of lung cancer vaccination, as well as the way they could be managed to pave the way for reaching the most optimized vaccine formulation.

Maintenance therapy with Everolimus in patients with refractory or relapsing Hodgkin lymphoma after autologous stem cell transplantation.

Introduction: Patients with relapsing or primary refractory Hodgkin lymphoma, still have unsatisfactory outcomes after high dose chemotherapy followed by autologous stem cell transplantation (ASCT). Brentuximab Vedotin (BV) is the only approved agent for maintenance therapy for up to one year in these patients, however, this agent is often not available or affordable for many patients, especially in the developing countries. In this study, we used Everolimus as maintenance therapy after ASCT among patients with relapsing/refractory Hodgkin lymphoma. Materials and Methods: We collected the data of 20 patients with primary refractory or relapsing Hodgkin lymphoma who had undergone ASCT between June 2016 and June 2021. Everolimus was started at 10 mg daily on day +90 after ASCT for at least two years in patients with stable disease status, confirmed by imaging modalities. Patients were followed for disease status and drug side effects every 3 months. Results: In our single-arm case-series study, the median duration of treatment was 22.95 months. Except for three patients, who had progression, others had no progression and are still receiving Everolimus (85%). No serious side effect was seen. We had no mortality due to disease recurrence. Conclusion: Until now, results showed promising effects of Everolimus in patients with relapsing or primary refractory Hodgkin lymphoma as maintenance therapy after ASCT.

Involvement Value of FLT-3, c-Myc, STAT3, p27, and HOTAIR Gene Expression in Acute Myeloid Leukemia Patients: A Molecular Perspective to a Novel Leukemogenesis Mechanism.

Background: The identification of long non-coding RNAs (lncRNAs) in the pathogenesis of acute myeloid leukemia (AML) has marked a new era in the molecular understating of the disease. This study investigated the correlation between the changes in the expression of lncRNAs, including HOTAIR, PVT-1, and CRNDE, and the alteration in the expression profile of FLT-3, c-Myc, STAT3, STAT5, and p27 in AML patients. Materials and Methods: Blood samples were collected from forty-one newly diagnosed AML patients and ten healthy individuals to evaluate the expression levels of the study genes using qRT-PCR analysis. The probable correlation between the gene expressions was determined using Pearson's correlation test. Results: The results showed that while there was a significant elevation in the expression of FLT3, c-Myc, STAT3, and HOTAIR, p27 expression remarkably diminished in AML patients compared to the control group. Also, a correlation was found between the expression of FLT-3 and p27 and the expression of HOTAIR and STAT3. It was assumed that FLT-3 had a role in increasing the proliferative and survival capacity of AML cells, at least partly, through c-Myc-mediated suppression of p27. Moreover, lncRNA HOTAIR showed to be involved in leukemia proliferation assumably by enhancing the expression of STAT3. Conclusion: Overall, the results of gene profile analysis suggested that studying the expression of HOTAIR, FLT-3, c-Myc, STAT3, and p27 could be helpful to AML patients, and each of these genes could be a valuable target for pharmaceutic intervention.

Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer worldwide. One of the chemotherapy agents, taxanes is important in increasing patients' survival. The purpose of this study is to assess the efficacy of taxane-based drugs versus non-taxanes in neoadjuvant chemotherapy in non-metastatic gastric adenocarcinoma (GA) in Iranian patients. MATERIALS AND METHODS: In a historical cohort method, 65 patients between 18 and 75 years old who suffered from non-metastatic GA were included. Nineteen and 21 and 25 patients, had undergone DCF (docetaxel, cisplatin, 5fluorouracil) and FLOT (5fluorouracil, leucovorin, oxaliplatin, docetaxel) and FOLFOX6 (oxaliplatin, leucovorin, 5fluorouracil) regimens, respectively, between 2018 and 2021. Survival criteria consisting of progression-free survival (PFS), overall survival (OS), progression rate, and mortality rate were evaluated using the Kaplan-Meier method, in a three-year follow-up period. RESULTS: The majority of patients were male (72.3%), with a median age of 65 years. Most of the patients had lesions with tumor, node, metastasis (TNM) stage IIIb (27.7%) and poor differentiated pathological grade (49.2%). OS time had a significant correlation with the low TNM stage (P = 0.01), well-differentiated pathological grade (P = 0.005), and FLOT vs. FOLFOX protocol (20.3 vs. 12.2 months, respectively. P =0.04). FLOT regimen had significantly better OS survival vs. DCF regimen (20.3 vs. 15.4 months, respectively, P = 0.03). No significant correlation was observed between survival criteria and other factors like gender, age, past medical history, Karnofsky scale, and tumor location in the stomach. The taxane-based arm (sum of DSF and FLOT) had no superiority over the non-taxane arm in survival criteria. CONCLUSION: FLOT protocol, as a taxane-based regimen had better survival compared to FOLFOX protocol in neoadjuvant chemotherapy in gastric non-metastatic adenocarcinoma.

Investigation of Expression Profile of Placenta-specific 1 (PLAC1) in Acute Myeloid and Lymphoid Leukemias.

Background: Placenta-specific 1 (PLAC1) is one of the cancer-testis-placenta antigens that has no expression in normal tissue except placenta trophoblast and testicular germ cells, but is overexpressed in a variety of solid tumors. There is a lack of studies on the expression of PLAC1 in leukemia. We investigated expression of PLAC1 in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). Methods: In this study, we investigated expression pattern of PLAC1 gene in peripheral blood and bone marrow mononuclear cells of newly-diagnosed patients with AML (n=31) and ALL (n=31) using quantitative real-time PCR. Normal subjects (n=17) were considered as control. The PLAC1 protein expression in the samples were also detected using western blotting. Results: Our data demonstrated that PLAC1 transcripts had 2.7 and 2.9 fold-change increase in AML and ALL, respectively, compared to normal samples. PLAC1 transcript expression was totally negative in all studied normal subjects. Level of PLAC1 mRNA expression in ALL statistically increased compared to normal samples (p=0.038). However, relative mRNA expression of PLAC1 in AML was not significant in comparison to normal subjects (p=0.848). Furthermore, relative mRNA expression of PLAC1 in AML subtypes was not statistically significant (p=0.756). PLAC1 gene expression showed no difference in demographical clinical and para-clinical parameters. Western blotting confirmed expression of PLAC1 in the ALL and AML samples. Conclusion: Considering PLAC1 expression profile in acute leukemia, PLAC1 could be a potential marker in leukemia which needs complementary studies in the future.

Breast cancer vaccination: Latest advances with an analytical focus on clinical trials.

Breast cancer (BC) is one of the main causes of cancer-related death worldwide. The heterogenicity of breast tumors and the presence of tumor resistance, metastasis, and disease recurrence make BC a challenging malignancy. A new age in cancer treatment is being ushered in by the enormous success of cancer immunotherapy, and therapeutic cancer vaccination is one such area of research. Nevertheless, it has been shown that the application of cancer vaccines in BC as monotherapy could not induce satisfying anti-tumor immunity. Indeed, the application of various vaccine platforms as well as combination therapies like immunotherapy could influence the clinical benefits of BC treatment. We analyzed the clinical trials of BC vaccination and revealed that the majority of trials were in phase I and II meaning that the BC vaccine studies lack favorable outcomes or they need more development. Furthermore, peptide- and cell-based vaccines are the major platforms utilized in clinical trials according to our analysis. Besides, some studies showed satisfying outcomes regarding carbohydrate-based vaccines in BC treatment. Recent advancements in therapeutic vaccines for breast cancer were promising strategies that could be accessible in the near future.

Evaluation of the Effect of Carvedilol in Preventing Right Ventricular Dysfunction in Breast Cancer Patients Receiving Anthracycline.

Background: Today, it has been shown that it is possible for right ventricular (RV) wall motion abnormalities or RV functional disorders to occur during cancer treatment. Now, considering the effect of carvedilol on beta 1, 2, and alpha receptors and its antioxidant properties, it seems that it can prevent RV abnormalities. Therefore, the aim of this study was to investigate the possible protective effects of carvedilol in preventing RV dysfunction in patients with breast cancer treated with anthracyclines. Materials and Methods: The present single-blind clinical trial study was performed on 23 patients with breast cancer that 12 of them received only the anthracycline antineoplastic doxorubicin (Adriamycin®) chemotherapy (control group) and 11 patients received carvedilol in addition to anthracycline. To evaluate the effect of carvedilol, patients underwent transthoracic echocardiography before intervention and 2 weeks after the end of treatment with anthracyclines. Results: The two parameters of RV ejection fraction and RV fractional area change in the carvedilol group with a mean of 66.41% ± 8.10% and 51.85% ± 6.89% were slightly higher than the control group with a mean of 64.58% ± 6.83% and 50.48 ± 5.79%, respectively, which was not statistically significant (P > 0.05). In contrast, RV S wave tissue Doppler imaging (S-TDI) in the control group with a mean of 0.13 ± 0.02 m/s was significantly lower than the carvedilol group with a mean of 0.14 ± 0.02 m/s (P = 0.022). Conclusion: According to the results of the present study, the effect of using carvedilol as a preservative on improving RV function was seen compared to the control group, although this difference was not statistically significant.

Proteome Analysis of Adult Acute Lymphoblastic Leukemia by Two-dimensional Blue Native/Sodium Dodecyl Sulfate Gel Electrophoresis.

Background: Despite the significant progress in the treatment of Acute Lymphoblastic Leukemia (ALL) in children, it still remains as one of the most challenging malignancies in adults. Identification of new biomarkers may improve the management of adult ALL. Proteins expressed on the cell surface can be considered as disease-associated biomarkers with potential for diagnosis and targeted therapies. Thus, membrane proteome studies give essential information about the disease-related biomarkers. Methods: We applied 2-dimensional blue-native SDS-PAGE technique followed by MALDI-TOF/TOF-mass spectrometry to study the cell membrane proteome of peripheral blood mononuclear cells of adult B-ALL patients in comparison to that of the healthy controls. Results: Sixty seven differentially expressed protein spots were detected, among them 52 proteins were found to be up-regulated but the other 15 proteins were down-regulated in B-ALL. Five differentially expressed proteins, involved in energy metabolism pathways, were detected in B-ALL patients compared to the healthy control group. Conclusion: Differentially expressed proteins provide an insight into the molecular biology of B-ALL. Further studies must be done to confirm our data to be considered as potential targets for detection and treatment of B-ALL.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Molecular pathways in glioblastoma-derived stem cells to identify effective drug agents: A bioinformatics study.

Background and Aim: Glioblastoma multiform (GBM) is considered as one of the malignant brain tumors that affect a wide range of people every year. Cancer stem cells, as essential factors, are resistant to chemotherapy drugs and complicate treatments. Therefore, finding critical molecular pathways in GBM-derived stem cells, and selecting the appropriate drug agents can prove more effective treatment approaches for GBM. Method: In this study, using RNA-Seq data, we performed continuous bioinformatics analyses and examined the up-and down-regulated genes from GBM-derived stem cells samples. Afterward, we separated the signaling pathways using the KEGG database and measured the protein interactions with the STRING database. Then, using the Drug matrix database, we nominated drugs that could affect these genes. Results: The first 20 pathways on tumorigenesis and 41 up-regulated and 73 down-regulated genes were selected. These genes were most active in the pathways involved in cell division, metabolism, cytoskeleton, cell adhesion molecules, and extracellular space. We then examined the candidate genes and the approach of the drugs that target these genes. Chlorambucil, cyclosporine A, doxorubicin, and etoposide were selected as the drug agents. Conclusion: Using integrated bioinformatics analyses, it was found that prominent genes in the cell cycle and cytoskeletal pathways are more expressed in cancer stem cells and that Chlorambucil, cyclosporine A, doxorubicin, and etoposide can be effective compounds to attenuate these cells.

Thoracic Sarcoma: A New Glance at the Epidemiological Characteristics of Disease in Iran from 2009 to 2014.

Background: The heterogeneity, high rate of mortality and lack of comprehensive diagnostic methods have categorized primary sarcomas of the thorax as a malignancy with dismal outcomes and unknown etiology. Given the fundamental role of epidemiological analysis in establishing management strategies, we designed a study with focus on the epidemiological characteristics of primary thoracic sarcomas in Iran. Methods: This national population-based cancer study was conducted on patients with histologically confirmed sarcoma of the thorax referred to the Iranian National Cancer Registry between 2009 and 2014. The incidence was calculated as number of cases per 100,000 person-years and was age-adjusted by the direct method using the weight of the 1960 world standard population. Results: Over a 6-year period, 1477 cases with pathologically confirmed thoracic sarcomas were registered in Iran, of which 896 were male and 581 were female. Khuzestan Province had the highest incidence of thoracic sarcomas as compared to other provinces. Malignant mesothelioma was the most common histological subtype (20.85%). Moreover, the age-standardized incidence rate (ASR) of the disease was 1.94 per 100,000 which was more common in males than females with the highest incidence rate in men aged more than 65 years. Conclusion: Our study provided valuable epidemiologic data on characteristics of thoracic sarcomas. This data can be used for strategizing preventive measures.

Investigating the molecular mechanisms of Tamoxifen on the EMT pathway among patients with breast cancer.

Tamoxifen is one of the most used drugs for breast cancer. This study aimed to investigate the effect of the Tamoxifen mechanism on the epithelial-mesenchymal transition (EMT) pathway among breast cancer patients due to its resistance to breast cancer cells. We selected the appropriate datasets from the GEO database using continuous and integrated bioinformatics analysis. We examined the signaling pathways, gene ontology, and protein association of genes after classifying the gene expression profile. Finally, we confirmed the candidate genes using the GEPIA database. Two groups were defined for gene expression profiles. The first group in which the expression profile of genes increased after Tamoxifen was evaluated using the expression profile of genes that decreased in the EMT pathway. The second group was the opposite of the first group. 253 genes in the first group and 302 genes in the second group were shared. The genes in the first group were involved in various pathways of cell death, focal adhesion, and cellular aging. The second group was more involved in different phases of the cell cycle. Finally, MYLK, SOCS3, and STAT5B proteins from the first group and BIRC5, PLK1, and RAPGAP1 proteins from the second group were selected as candidate proteins in connection with the effect of Tamoxifen on the EMT pathway. We evaluated Tamoxifen's effect on the EMT pathway more accurately. However, for a closer look at Tamoxifen, more studies need to be done on target genes and proteins to clarify their role.

The Prevalence of Early Toxoplasmosis after Bone Marrow Transplantation Using PCR: A Study in Iranian Patients.

BACKGROUND: In immuno-compromised organ transplant recipients, toxoplasmosis can be caused by either an infected graft or a latent infection, during which transformation from a chronic state to an active infection (reactivation) is observed. PCR is an accurate and sensitive molecular method widely used in medical sciences, especially in diagnostic procedures. OBJECTIVE: The aim of this study was to determine the prevalence of early toxoplasmosis infection in bone marrow transplant patients by PCR. METHODS: The blood samples of 50 patients with hematological disorders who had received bone marrow transplants were collected using a standard phlebotomy technique. To evaluate antitoxoplasma antibodies, we utilized the enzyme-linked immunosorbent assay (ELISA) method using a specific commercial kit (Akon) based on the manufacturer's instructions. Genomic DNA extracted from toxoplasma tachyzoite was used as the template for PCR. RESULTS: 22 (44%) patients were women, and 28 (56%) were men. There were no significant differences in the distribution of genders and age groups in patients with various cancers. Antitoxoplasma IgG was positive in 39 patients, while none of them were IgM positive. According to PCR results, 5 patients were positive for toxoplasmosis. All of the PCR-positive cases (2 with AML, 2 with HL, and 1 with AA) had successful engraftment at 40 days post-transplantation. CONCLUSION: Because of the higher efficacy of PCR in the diagnosis of toxoplasmosis, using this method along with other routine diagnostic modalities in this condition is recommended. PCR-based techniques can also be utilized to periodically determine parasite load in blood after transplantation.

Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

Association Between Human Leukocyte Antigens and Graft-Versus-Host Disease Occurrence in Allogeneic Hematopoietic Stem Cell Transplantation - A 10-Year Experience on Iranian Patients.

BACKGROUND: Human leukocyte antigen (HLA) molecules mediate critical roles in determining responsiveness or non-responsiveness of the immune system, especially in transplantation. Some studies have shown a possible association between certain HLA alleles and some allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes such as acute/chronic graft-versus-host disease (aGVHD/cGVHD) and overall survival (OS). In the current study, we investigated any possible association of HLA subclasses and acute/chronic GVHD occurrence as well as OS in patients receiving HLA-matched sibling allo-HSCT. METHODS: We retrospectively evaluated the association of various HLA alleles with the incidence of aGVHD, cGVHD, and OS of 162 patients who received allo-HSCT from HLA-matched sibling between 2009-2018 at Taleghani hospital in Tehran. RESULTS: We found that the incidence of aGVHD grades II-IV was higher among patients who had HLA-B*07 (P=0.031) and HLA-DRB1*07 (P=0.052). The presence of HLA-A*01 was associated with 4.5-fold greater odds of incidence in the extensive-type of cGVHD (P=0.009). Furthermore, HLA-A*03 (P=0.089), HLA-B*13(P=0.013), HLA-B*40 (P=0.042), HLA-DRB1*02 (P=0.074), and HLA-DRB1*04 (P=0.039) were associated with a lower rate of OS. CONCLUSION: This study suggests that certain HLA alleles might influence the incidence and severity of acute or chronic GVHD in the context of HLA-matched sibling allo-HSCT. In addition, some specific HLA alleles help predict OS in allo-HSCT recipients. These results might be helpful in estimating the incidence of aGVHD, cGVHD, and OS as well as designing personalized therapy.

Immunohistochemical Expression Pattern of MLH1, MSH2, MSH6, and PMS2 in Tumor Specimen of Iranian Gastric Carcinoma Patients.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related death. Determining molecular and histopathologic tumor features, which may contribute to the development or progression of gastric cancer, can improve the prognosis. Expression patterns of DNA repair proteins such as MLH1, MSH2, MSH6, and PMS2 that are associated with microsatellite instability (MSI) are some of the markers that are useful in predicting the prognosis of gastric cancer. PURPOSE: The purpose was to determine the immunohistochemical expression pattern of MLH1, MSH2, MSH6, and PMS2 in tumor specimens of Iranian gastric carcinoma patients. METHODS: In this prospective cohort, 186 consecutive patients with gastric cancer, attending Taleghani Hospital, were enrolled. The immunohistochemical expression patterns of MLH1, MSH2, MSH6, and PMS2 in tumor specimens among them were determined. RESULTS: The results of this study demonstrated that 91.4% of our gastric cancer patients were negative for MSI, and 8.6% of them were MSI positive. The positive MSI was seen in 5.9% and 15.7% of male and female subjects, respectively, with a significant difference (P = 0.043). The other variables were not related to MSI results (P > 0.05). CONCLUSION: According to the obtained results, the expression of MLH1, MSH2, MSH6, and PMS2 in tumor specimens is positive in 8.6% of the total Iranian gastric cancer sample size, which is mainly positive in female subjects. However, it is not related to the location and stage of the tumor.

Resistance to immunotherapy in human malignancies: Mechanisms, research progresses, challenges, and opportunities.

Despite remarkable advances in different types of cancer therapies, an effective therapeutic strategy is still a major and significant challenge. One of the most promising approaches in this regard is immunotherapy, which takes advantage of the patients' immune system; however, the many mechanisms that cancerous cells harbor to extend their survival make it impossible to gain perfect eradication of tumors. The response rate to cancer immunotherapies, especially checkpoint inhibitors and adoptive T cell therapy, substantially differs in various cancer types with the highest rates in advanced melanoma and non-small cell lung cancer. Indeed, the lack of response in many tumors indicates primary resistance that can originate from either tumor cells (intrinsic) or tumor microenvironment (extrinsic). On the other hand, some tumors show an initial response to immunotherapy followed by relapse in few months (acquired resistance). Understanding the underlying molecular mechanisms of immunotherapy resistance makes it possible to develop effective strategies to overcome this hurdle and boost therapy outcomes. In this review, we take a look at immunotherapy strategies and go through a number of primary and acquired resistance mechanisms. Also, we present various ongoing methods to overcoming resistance and introduce some promising fields to improve the outcome of immunotherapy in patients affected with cancer.

Anticancer Effects of ZnO/CNT@Fe3O4 in AML-Derived KG1 Cells: Shedding Light on Promising Potential of Metal Nanoparticles in Acute Leukemia.

Background: Therapeutic approaches for acute myeloid leukemia (AML) have remained largely unchanged for over 40 years and cytarabine and an anthracycline (e.g., daunorubicin) backbone is the main induction therapy for these patients. Resistance to chemotherapy is the major clinical challenge and contributes to short-term survival with a high rate of disease recurrence. Given the established efficacy of nanoparticles in cancer treatment, this study was designed to evaluate the anticancer property of our novel nanocomposite in the AML-derived KG1 cells. Materials and Methods: To assess the anti-leukemic effects of our nanocomposite on AML cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of nanocomposite on cell cycle and apoptosis. Results: Our results outlined that ZnO/CNT@Fe3O4 decreased viability and metabolic activity of KG1 cells through induction of G1 arrest by increasing the expression of p21 and p27 cyclin-dependent kinase inhibitors and decreasing c-Myc transcription. Moreover, ZnO/CNT@Fe3O4 markedly elevated the percentage of apoptotic cells which was coupled with a significant alteration of Bax and Bcl-2 expressions. Synergistic experiments showed that ZnO/CNT@Fe3O4 enhances the cytotoxic effects of Vincristine on KG1 cells. Conclusion: In conclusion, this study sheds light on the potent anti-leukemic effects of ZnO/CNT@Fe3O4 and provides evidence for the application of this agent in the treatment of acute myeloid leukemia.

Primary squamous cell carcinoma of the liver: a case report.

Primary squamous cell carcinoma (SCC) of the liver is rare and has an extremely poor prognosis. It is very difficult to detect and is sometimes misdiagnosed. It has been reported that male sex, hepatic cyst, hepatolithiasis, hepatic teratoma, and liver cirrhosis may be associated with SCC of the liver. A 67-year-old woman was admitted to our hospital with anorexia, weakness, and right upper quadrant abdominal (RUQ) pain. Sonography and an abdominal computed tomography scan revealed a 36 × 34 cm mass in the liver. Pathological analysis of the sample suggested SCC. According to the negative radiographic findings in other major organs, the tumor was considered primary. The patient was treated with surgical resection and followed by palliative care. Our case died 5 months after the initial presentation.