Prolonged Survival Period Research Articles

DDDR-03. DEVELOPMENT OF ANTI-TUMOR AROMA THERAPY FOR GLIOBLASTOMA WITH LEMONGRASS ESSENTIAL OIL

Abstract INTRODUCTION Aroma essential oils apply to cancer therapy because of their immune-enhancing and sedative effects, and their ability to reduce the side effects of chemotherapy. Recently, aroma essential oils have also been reported to have anti-tumor effects. We investigate the anti-tumor effects of aromatic compounds contained in essential oils as a novel treatment for glioblastoma. In this study, we analyzed the antitumor effect of lemongrass essential oil and investigated its antitumor aroma therapy for glioblastoma. methods and RESULTS Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used in the study. Tumor cells were cultured in the presence of lemongrass essential oil for 72 hours, and the growth inhibitory effect was observed, suggesting that the evaporated lemongrass essential oil components acted on tumor cells in the vicinity. In addition, a similar effect was observed with citral alone, which is the main component of lemongrass. Analysis of the effects of citral revealed that citral strongly binds to MARK4 and inhibits its enzyme activity, and that citral decreases the phosphorylation of tau protein. Next, a mouse brain tumor model with RSV-M was established, and the anti-tumor effect of lemongrass essential oil was studied. The results showed that the mice that inhaled lemongrass essential oil for 12 h/day had a significantly prolonged survival period compared to the control group. DISCUSSION Citral is the main component of lemongrass essential oil, which contains 70-80% of lemongrass essential oil. This study suggests a mechanism of inhibition of tumor cell proliferation by citral in malignant gliomas. Citral is a volatile monoterpene, and its anti-tumor effect was demonstrated by diffusion through evaporation. CONCLUSION Citral in lemongrass essential oil shows anti-tumor effects and is expected to be applied to a new glioblastoma therapy using “aroma”

Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population.The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses.Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

Breeding for Bacterial Wilt Disease Resistance in Brinjal

Brinjal is a warm–season vegetable that belongs to the Solanaceae family. Among the biotic stresses of brinjal, bacterial wilt is a major disease caused by a soil-borne bacterium, Ralstonia solanacearum. Both cultural and chemical disease control methods are not effective due to the wide host range and prolonged spore survival periods in soil. In recent past, the use of resistant varieties and hybrids are recognized as the effective method to control bacterial wilt disease. Information on genetics of resistance to bacterial wilt disease is of prime importance for improvement of varieties and hybrids in brinjal. The bacterial wilt resistance response and resistance mechanisms are strictly based on the environmental conditions and cultivars. In traditional crop improvement methods, the development of varieties and hybrids is expensive and time consuming. The discovery of molecular marker systems increases the speed and precision for developing of varieties and hybrids with desired agronomic traits.

Does Use of Intratumoral Injections in Solid Tumor Malignancies Improve Outcomes and Reduce Adverse Events? An Integrative Review.

The purpose of this review is to assess the efficacy and adverse events associated with intratumoral injection in the treatment of solid tumor malignancies. A literature review was conducted using PubMed, the Cochrane Database of Systematic Reviews, CINAHL, and Scopus databases from 2009 to 2022. A total of 588 articles were retrieved, with five selected based on inclusion and exclusion criteria. Inclusion criteria specified English language publications, in human trials, and use of intratumoral anticancer agents. The findings from this integrative review demonstrate treatment efficacy as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with increased stable disease and partial response in patients as well as a prolonged survival period. Additionally, findings show that this therapy is associated with predominantly mild adverse events.

Zuogui pill disrupt the malignant cycle in breast cancer bone metastasis through the Piezo1-Notch-1-GPX4 pathway and active molecules fishing

Background: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis.Purpose: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing.Methods: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP.Results: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein.Conclusion: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.

Establish a whole-process comprehensive surveillance management mode for immune checkpoint inhibitor pneumonitis

The application of immune checkpoint inhibitors (ICIs) has shown impressive anti-tumor efficacy across multiple malignant tumors, leading to the prolonged survival period of tumor patients. However, immune-related adverse events should not be ignored. Checkpoint inhibitor pneumonitis (CIP) is a pulmonary adverse event that can occur in malignant tumor patients after receiving ICIs treatment. The incidence of CIP has been reported to range from 2.7% to 20.0% in clinical trials and real-world research. Furthermore, some patients might suffer from serious or fatal CIP, and the prognosis of such patients will be poor. Early detection, diagnosis and treatment may improve the prognosis of these patients. The establishment of a whole-process CIP comprehensive surveillance management mode covering the health care system and patients during ICIs treatment might be helpful to improve the early diagnosis and treatment capacity of CIP, which is a key measure to improve the prognosis of these patients.

N-acetyl-galactosamine modified metal-organic frameworks to inhibit the growth and pulmonary metastasis of liver cancer stem cells through targeted chemotherapy and starvation therapy

Hepatocellular carcinoma (HCC) is a common high-mortality malignancy which still needs efficient treatments. HCC patients undergoing extrahepatic metastases are mostly with unsatisfactory prognosis. Therefore, specific attention has been paid to extrahepatic HCC metastasis. We integrated Sorafenib (Sor) and glucose oxidase (GOx) into a N-acetyl-galactosamine (GalNAc) modified zeolitic imidazolate framework (ZIF-8), designated as SG@GR-ZIF-8, for targeted bimodal therapies of chemotherapy and starvation therapy against HCC. The hepatic delivery of SG@GR-ZIF was mediated by the specific recognition of GalNAc residues with asialoglycoprotein (ASGPR) on the liver cell surface. Sor is a clinically approved anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. GOx can efficiently induce cell death and disturb malignant progression by suppressing glucose supply of cancer cells, which is highly associated with metabolic rewiring in metastasis. The nano-formulation exhibit significant anti-metastatic HCC activity against C5WN1 cells, a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In a subcutaneous C5WN1-tumor carrying mouse model, SG@GR-ZIF exhibits potent synergistic anti-tumor activity with a tumor inhibition rate of 89% and a prolonged survival status. The growth and pulmonary metastasis of HCC in an orthotopic mouse model of HCC was remarkably suppressed in SG@GR-ZIF treated group. The therapeutic strategy targeting energy supply combined with first-line treatment holds great promise for the future treatment of metastatic HCC. Statement of significanceSG@GR-ZIF, a N-acetyl-galactosamine modified metal-organic framework carrying Sorafenib and glucose oxidase, was fabricated for treating metastatic hepatocellular carcinoma (HCC). Sorafenib is an anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. Glucose oxidase blocks energy demand in HCC metastasis by depleting glucose. C5WN1 was used for therapeutic evaluations as a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In subcutaneous C5WN1-tumor bearing mice, SG@GR-ZIF exhibited a tumor inhibition rate of 89% and prolonged survival period. In orthotopic C5WN1-tumor carrying mice, the growth and pulmonary metastasis of hepatocarcinoma was remarkably suppressed by SG@GR-ZIF. Together, this study suggests the great potential of synergistic chemo/starvation therapy mediated by SG@GR-ZIF for treating metastatic HCC.

Biomimetic Activator of Sonodynamic Ferroptosis Amplifies Inherent Peroxidation for Improving the Treatment of Breast Cancer.

Ferroptosis is a type of nonapoptotic cell death and is gradually emerging as an important anticancer treatment. However, its therapeutic efficacy is impaired by low intracellular levels of reactive oxygen species (ROS) and long-chain polyunsaturated fatty acids, significantly limiting its therapeutic potential. Herein, a multimodal strategy to improve ferroptosis is presented, in which a state-of-art engineered erythrocyte, termed as sonodynamic amplified ferroptosis erythrocyte (SAFE), is developed for simultaneously activating ferroptosis and oxygen-riched sonodynamic therapy (SDT). SAFE is composed of internalizing RGD peptide and red blood cell membrane hybrid camouflaged nanocomplex of hemoglobin, perfluorocarbon, ferroptosis activator (dihomo-γ-linolenic acid, DGLA), and sonosensitizer verteporfin. It is identified that SAFE, under ultrasound stimulation, can not only substantially supply oxygen to overcome tumor hypoxia associated therapeutic resistance, but effectively activate ferroptosis through the coeffect of SDT triggered ROS production and DGLA mediated lipid peroxidation. In vivo studies reveal that SAFE selectively accumulates in tumor tissues and induces desirable anticancer effects under mild ultrasound stimulation. Importantly, SAFE can effectively inhibit tumor growth with minimal invasiveness, resulting in a prolonged survival period of mice. Therefore, a multimodal ferroptosis therapy driven by oxygen-riched sonodynamic peroxidation of lipids, significantly advancing synergistic cancer treatment, is presented.

Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options.

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

Antitumor Effect of Sclerostin against Osteosarcoma.

Simple SummaryOsteosarcoma is highly variable and heterogeneous, which is one of the reasons for its resistance to treatment. Because osteosarcoma is defined by abnormal bone formation, we hypothesize its suppression could lead to effective treatment for all types of osteosarcomas. Sclerostin is secreted by osteocytes and inhibits the canonical pathway by binding to LRP5/6, thereby suppressing bone formation. The resulting suppression of bone formation leads to bone loss and osteoporosis. Here, we investigated the antitumor effect of sclerostin against osteosarcoma and found that sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells.Various risk factors and causative genes of osteosarcoma have been reported in the literature; however, its etiology remains largely unknown. Bone formation is a shared phenomenon in all types of osteosarcomas, and sclerostin is an extracellular soluble factor secreted by osteocytes that prevents bone formation by inhibiting the Wnt signaling pathway. We aimed to investigate the antitumor effect of sclerostin against osteosarcoma. Osteosarcoma model mice were prepared by transplantation into the dorsal region of C3H/He and BALB/c-nu/nu mice using osteosarcoma cell lines LM8 (murine) and 143B (human), respectively. Cell proliferations were evaluated by using alamarBlue and scratch assays. The migratory ability of the cells was evaluated using a migration assay. Sclerostin was injected intraperitoneally for 7 days to examine the suppression of tumor size and extension of survival. The administration of sclerostin to osteosarcoma cells significantly inhibited the growth and migratory ability of osteosarcoma cells. Kaplan–Meier curves and survival data demonstrated that sclerostin significantly inhibited tumor growth and improved survival. Sclerostin suppressed the proliferative capacity and migratory ability of osteosarcoma cells. Osteosarcoma model mice inhibited tumor growth and prolonged survival periods by the administration of sclerostin. The effect of existing anticancer drugs such as doxorubicin should be investigated for future clinical applications.

Undifferentiated carcinoma with osteoclastic giant cells of pancreas: Case report and brief literature review

Undifferentiated carcinoma with osteoclastic giant cells is a distinctive rare neoplasm involving pancreas and rarely bile ducts. This neoplasm shows characteristic histologic features with variable admixture of mononuclear histiocytic cells, non- neoplastic osteoclastic giant cells and neoplastic mononuclear cell component. Though, this tumor has been shown to share genetic alterations with pancreatic ductal adenocarcinoma, clinically, it behaves unpredictably with a substantial proportion of patient showing prolonged survival period. We present a case of this rare pancreatic tumour with brief literature review discussing the key pathologic features, immunophenotype, genetic profile and clinical behavior. Undifferentiated carcinoma with osteoclastic giant cells is a rare neoplasm in pancreas which is believed to be of epithelial origin and shares genetic aberrations with ductal adenocarcinoma. Despite this, these tumours have better prognosis with prolonged survival period.

A Real World Study of Venetoclax Combined with Azacitidine in 64 Chinese Patients Newly Diagnosed Acute Myeloid Leukemia

Background: Venetoclax combined with azacitidine has been demonstrated to have a favorable overall response rate and tolerable safety in acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy.Methods: This study retrospectively recruited 64 Adults (≥18 years) with newly diagnosed AML ineligible for intensive chemotherapy who had received at least one cycle of treatment with venetoclax plus azacitidine. The primary endpoint was overall survival (OS). Secondary endpoints were remission rates. Safety was evaluated based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.Results: The median age of the enrolled patients was 69 years. The median OS for the cohort was 15.5 months, with 21.2 months for complete responders as opposed to 13.3 months for those who did not achieve a complete response. 39 (60.9%) patients achieved composite complete remission (completeremission (CR) + CR with incomplete count recovery (CRi)) and 7/64 (10.9%) achieved morphologic leukemia-free state (MLFS) with a median follow-up time of 14.7 months. The median CR+CRi duration was 10.9 months. It is noteworthy that 43/64 (67.2%) patients achieved the best response after one cycle with a median time of 1.2 months. Normal karyotype (P=0.015) was significantly associated with extended OS in multivariate analysis, while higher white blood cell count (P=0.032), lower platelet count (p=0.018) and antifungal drug combination (P=0.013) were predictors of shortened OS in univariate analysis. Common grade 3/4 Adverse Events (AEs) included infection (68%) and hematological AEs consisting of neutropenia (93%), anemia (90%), leukopenia (86%), thrombocytopenia (77%) and febrile neutropenia (52%). The median neutropenia duration was 16 days.Conclusions: The novel venetoclax-azacitidine combination regimen showed prolonged survival period, promising efficacy, sound and rapid response, and superior tolerance in Chinese patients newly diagnosed AML. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Novel Antiplasmodial Compounds Leveraged with Multistage Potency against the Parasite Plasmodium falciparum: In Vitro and In Vivo Evaluations and Pharmacokinetic Studies.

Hydroxyethylamine (HEA)-based novel compounds were synthesized and their activity against Plasmodium falciparum 3D7 was assessed, identifying a few hits without any apparent toxicity. Hits 5c and 5d also exhibited activity against resistant field strains, PfRKL-9 and PfC580Y. A single dose, 50 mg/Kg, of hits administered to the rodent parasite Plasmodium berghei ANKA exhibited up to 70% reduction in the parasite load. Compound 5d tested in combination with artesunate produced an additional antiparasitic effect with a prolonged survival period. Additionally, compound 5d showed 50% inhibition against hepatic P. berghei infection at 1.56 ± 0.56 μM concentration. This compound also considerably delayed the progression of transmission stages, ookinete and oocyst. Furthermore, the toxicity of 5d assessed in mice supported the normal liver and kidney functions. Altogether, HEA analogues (5a-m), particularly 5d, are nontoxic multistage antiplasmodial agents with therapeutic and transmission-blocking efficacy, along with favorable preliminary pharmacokinetic properties.

ITGA2, LAMB3, and LAMC2 may be the potential therapeutic targets in pancreatic ductal adenocarcinoma: an integrated bioinformatics analysis

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM–receptor interaction, and focal adhesion signaling. The protein–protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan–Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.

Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose.

Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.

Abdominal cryptococcosis in dogs and cats: 38 cases (2000‐2018)

To report the clinical presentation, laboratory and imaging findings, treatment and outcome of abdominal cryptococcosis in dogs and cats in Australia. Canine and feline cases from Australia were retrospectively identified (2000 to 2018) via laboratory and referral centre searches for abdominal cryptococcosis diagnosed by cytology (needle aspirates) or histopathology (biopsy or necropsy) of abdominal organs/tissues. Signalment, presenting complaints, clinical signs, laboratory findings, medical imaging, latex cryptococcal antigen agglutination test (LCAT) titres, treatment and outcome data was collected. Thirty-eight cases were included (35 dogs, three cats) in the study. Median age of presentation was 2 years for dogs and 6 years for cats. Common presenting complaints included vomiting (23/38), lethargy (19/38) and inappetence/anorexia (15/38). Abdominal ultrasound (25/38 cases) revealed mesenteric and intestinal lesions in most of the cases. On surgical exploration, seven cases had an intestinal lesion associated with an intussusception. Nineteen cases had a pre-treatment LCAT performed, with a median initial titre of 1:2048 (range 1:2 to 65,536). Twenty-four cases (23 dogs, one cat) received treatment, either medical, surgical or both. Median survival time for cases with combined medical and surgical treatment, surgical treatment alone or medical treatment alone was 730, 140 and 561 days, respectively. Eleven remain alive at the time of follow up. Abdominal cryptococcosis although rare should be a considered as a diagnostic possibility in an especially young dog presenting with gastro-intestinal signs. Older dogs can also present with this condition and should not be euthanised based on imaging alone due to the likenesses with neoplasia. With appropriate treatment and monitoring many dogs may have a prolonged survival period and some may be cured.

Recombination Monophosphoryl Lipid A-Derived Vacosome for the Development of Preventive Cancer Vaccines.

Recently, there has been an increasing interest for utilizing the host immune system to fight against cancer. Moreover, cancer vaccines, which can stimulate the host immune system to respond to cancer in the long term, are being investigated as a promising approach to induce tumor-specific immunity. In this work, we prepared an effective cancer vaccine (denoted as “vacosome”) by reconstructing the cancer cell membrane, monophosphoryl lipid A as a toll-like receptor 4 agonist, and egg phosphatidylcholine. The vacosome triggered and enhanced bone marrow dendritic cell maturation as well as stimulated the antitumor response against breast cancer 4T1 cells in vitro. Furthermore, an immune memory was established in BALB/c mice after three-time preimmunization with the vacosome. After that, the immunized mice showed inhibited tumor growth and prolonged survival period (longer than 50 days). Overall, our results demonstrate that the vacosome can be a potential candidate for clinical translation as a cancer vaccine.

Patient-Reported Quality-of-Life Outcome Measures in the Thyroid Cancer Population.

Background: There is an escalating worldwide population of thyroid cancer (TC) survivors. In addition to conventional metrics of quality of care, quality-of-life (QoL) assessment in TC patients is imperative. TC survivors face unique impediments to health-related quality of life (HRQoL), including thyroid-specific symptoms and exposure to disease-related stressors-including fear of recurrence and financial toxicity-over a prolonged survival period. Survey instruments currently used to assess HRQoL in TC survivors may be insufficient to accurately capture the burden of disease in this population. We aimed to identify the HRQoL instruments in the literature, which have been applied in the TC survivor population, and to present the psychometric properties of the scales and indexes that have been used. We hypothesized that few instruments have shown evidence of validity in this population. Summary: Of the 927 articles identified by search criteria, only 28 studies using 15 HRQoL instruments met inclusion criteria. Of the 15 HRQoL instruments identified, 9 were psychometric health status instruments and 6 were preference-based indexes, but none had been validated in the TC survivor population. While the majority of reviewed studies demonstrated impaired psychological and emotional well-being in TC survivors, these findings were not uniformly demonstrated across studies, and the longevity of the impact of TC on HRQoL was variably reported. Conclusions: Discrepancies in the literature regarding the impact of TC survivorship on HRQoL emphasize the challenges of accurately assessing patient perspectives, reinforcing the importance of using well-constructed instruments to measure patient-reported outcomes in the target population. Care providers involved in the treatment of TC survivors should be aware of longitudinal effects on HRQoL, especially pertaining to chronic psychological debilitation. Further development and rigorous validation of TC-specific instruments will allow for better data gathering and understanding of the barriers to achieving high long-term HRQoL in TC survivors throughout their long postsurvival course.

Association between Shoulder Range of Motion and Pain Catastrophizing Scale in Breast Cancer Patients after Surgery

Background: Prolonged survival period as a result of early diagnosis and treatment in breast cancer has increased the importance of postoperative morbidities. The aim of the present study was to investigate the association of pain ca­tastrophizing with shoulder pain in patients with decreased shoulder range of motion in the postoperative period. Patients and Methods: The present study included 53 patients who underwent surgery due to breast cancer. Patients who had bilateral mastectomy, distant metastases, cervical-cranial originated lesions, patients with problems involving one of the shoulders or upper extremities before the operation, and patients with cognitive impairment, heart failure, or low albumin levels (liver parenchyma disease or renal failure) were excluded. Shoulder range of motion was measured in the postoperative period, and two study groups were established: one with a limited shoulder range of motion level and the other with a normal level. Effects of pain catastrophizing and shoulder pain severity on shoulder range of motion limitation were compared between the two groups. Results: The average age of 53 female patients who had breast surgery was 52.3 ± 10.5 years. In the group with limited shoulder range of motion, the median pain catastrophizing scale value was 27 (range 5–32) and the shoulder pain severity score was 4 (range 0–8), while in the group with normal shoulder range of motion these values were 11 (range 3–39) and 2 (range 0–6), respectively (p < 0.05). In addition, it was found that factors such as surgical treatment modality and postoperative radiotherapy did not significantly affect shoulder range of motion limitation. Conclusion: Determining the pain catastrophizing scale of patients and controlling pain in the early postoperative period could have positive effects on shoulder range of motion.

Devitalization of the immune mapped protein 1 undermines the intracellular proliferation of Toxoplasma gondii

The intracellular protozoan Toxoplasma gondii infects approximately one-third of the world's population as well as various animals, causing toxoplasmosis. However, there remains a need to define the functions of newly identified genes of T. gondii. In the present study, a novel molecule, immune mapped protein 1 of T. gondii (TgIMP1), was devitalized by CRISPR/Cas9 system to investigate the phenotypic changes of the parasite. We found that the virulence of ΔTgIMP1 knockout strain was reduced in comparison with wild-type GT1 tachyzoites, showing a statistically decreased plaque in HFF cells and a significantly prolonged survival period of mice (P < 0.05). Moreover, the data of phenotype analyses in vitro showed a different level of the intracellular proliferation and the subsequent egress between ΔTgIMP1 and wild-type GT1 strain (P < 0.05); while no statistically significant difference was detected during the process of attachment or invasion. These results suggested that TgIMP1 is closely associated with the intracellular proliferation of this parasite.