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The understanding of the nature of catecholamine-secreting tumors has changed significantly in recent years, affecting terminology and classification. Phaeochromocytoma/paraganglioma (PCC/PG) is a rare neuroendocrine tumor from chromaffin tissue that produces and secretes catecholamines. The incidence of PCC/PG is relatively low, with 2–8 cases per 1 million population per year; among patients with arterial hypertension, their prevalence is 0.2–0.6%. However, delayed diagnosis of PCC/PG is associated with a high risk of cardiovascular complications and a high mortality rate. The consensus presents the clinical manifestations of the disease with an emphasis on the course of arterial hypertension as the most common symptom in PCC/PG; modern ideas about the features of diagnosis, aspects of preoperative preparation, treatment, and follow-up of patients with PCC/PG are considered.

Colorectal cancer typically metastasizes to the peritoneum, liver, and lungs. However, metastases to the fallopian tube and uterus are uncommon. This case report delves into this rare occurrence of metastasis and discusses its characteristics, diagnostic methods, and treatments based on an extensive literature review. We present the case of a 61-year-old female patient who underwent her initial hospitalization for da Vinci robotic surgery to address colorectal cancer, stage pT3N0M0. However, during routine postoperative follow-up 6 months later, a localized rectal recurrence was detected. The patient commenced chemoradiotherapy with full response. Subsequently, the patient was readmitted due to pelvic pain again, and a magnetic resonance imaging scan revealed an abnormal mass in the patient's left fallopian tube and uterine corpus, infiltrating the myometrium. Consequently, total hysterectomy with bilateral adnexectomy was performed, along with omentectomy, which confirmed metastatic involvement from rectal cancer upon postoperative pathological examination. This case may inform further diagnosis and treatment of colorectal cancer metastasis to the fallopian tube. [ABSTRACT FROM AUTHOR]

Copyright of Current Retina Journal / Güncel Retina Dergisi is the property of Anadolu Kitabevi Basim Yayim Medikal Turizm Kirtasiye Tic. Ltd. Sti. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Current Retina Journal / Güncel Retina Dergisi is the property of Anadolu Kitabevi Basim Yayim Medikal Turizm Kirtasiye Tic. Ltd. Sti. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose of the study. Elaboration of a surgical technique to manage patients with metastatic lesions of the craniovertebral region.Patients and methods. The study included 7 patients with metastatic lesions of the craniovertebral region, who’ve been operated on for severe instability, pain syndrome, neurological deficit in the period from 01/01/2014 to 09/30/2022. To assess the neurological status and patients’ condition the Frankel and Karnofsky scales were used on the day of admission and discharge of the patients from the hospital. Pain intensity was assessed using a visual analog pain scale (VAS). To assess instability in the affected spinal motion segment the SINS scale was used. All patients underwent palliative surgical treatment in the amount of occipitospondylodesis with a biopsy of the neoplasm from the posterior approach.Results. The average age of patients was 60 [44; 66] years. All patients had a marked pain syndrome prior to the surgery. The average pain intensity according to the visual analog pain scale was 8 points. In the preoperative period, 6 (85 %) patients on the Frankel scale were assigned to group E, 1 (14 %) – to group C. In 6 (85 %) patients there was no dynamics in the neurological status following the surgery, however according to the Karnofsky scale there was an improvement up to 10 points due to the regression of the pain syndrome down to 1 point on the visual analog scale. Hemiparesis developed in 1 (14 %) patient due to malposition of the laminar hook in the postoperative period. The average duration of surgical interventions made up 337.5 [315; 345] min, the average intraoperative blood loss made up 300 [300; 800] ml. In 6 out of 7 patients (85 %) there was no neurological status dynamics after the surgery, and according to the Karnofsky scale an improvement up to 10 points was noted due to regression of the pain syndrome to an average value of 1 [1; 2] VAS score. Conclusion. The obtained results indicate the clinical application possibilities of minimally traumatic surgical technologies for the treatment of craniovertebral zone metastatic tumors.

Introduction: Lungs are one of the most common sites for metastatic tumors in the body. In addition, primary lung tumors are the most common cause of death due to neoplasms in both genders. Treatment strategies are completely different for primary and metastatic lung tumors making accurate diagnosis of lung tumors an effective factor in planning the correct treatment. The development of personalized medicine and targeted therapy, especially in the treatment of primary lung tumors, has highlighted the importance of correct diagnosis of these tumors. Case report: The Pathology Center of Imam Khomeini Hospital Cancer Institute in Tehran, Iran, as a referral center for cancer across the country, is faced with a large number of lung biopsies, and therefore, there will be numerous diagnostic challenges. In this article, we presented two cases of primary female genital tract (cervical) tumors that during follow up lung masses were detected. Diagnosis on lung biopsy assigned as primary lung adenocarcinoma. Both cases referred to our lab for second opinion accompanied with related resected sample and implementation of further supplementary markers documented metastatic origin of tumors. Discussion & conclusion: In both cases, similarity in immunohistochemical characteristics of metastatic tumors with primary lung adenocarcinoma, especially positive nuclear TTF1 staining led to misdiagnosis of lung tumor origin. This finding emphasizes on the use of other specific markers related to primary site of tumor to decrease possibility of incorrect diagnosis of the origin of the tumor in metastatic setting. Due to remarkable influence of primary versus metastatic origin of lung tumor on selection of treatment, pathologists should be considered correct diagnosis and notice to similarity of immunohistochemical markers of primary lung tumors to other organs and implementation of more specific markers are necessary.

Brain metastasis (BrM) is the most common form of brain cancer, characterized by neurologic disability and an abysmal prognosis. Unfortunately, our understanding of the biology underlying human BrMs remains rudimentary. Here, we present an integrative analysis of >100,000 malignant and non-malignant cells from 15 human parenchymal BrMs, generated by single-cell transcriptomics, mass cytometry, and complemented with mouse model- and in silico approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and revealed stromal immunosuppressive states enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental traits.

The orofacial region may be the first site for the dissemination of malignancies from the remote regions in the jawbones. The most common location of metastatic lesions in the jawbones is the mandible, with the molar region the most frequently involved site. Radiotherapy, chemotherapy, and surgical resection can be an approach in the treatment protocol depending upon patient age and growth of tumor mass. This case report presents a case of follicular variant thyroid carcinoma, infiltrative type, pT1bN0Mx with mandibular metastasis affecting both hard and soft tissue in a 55-year-old female. [ABSTRACT FROM AUTHOR]

The number of advanced-age patients with spinal metastases is rising. This study was performed to clarify the characteristics and surgical outcomes of spinal metastases in advanced-age patients. We prospectively analyzed 216 patients with spinal metastases from 2015 to 2020 and divided them into three age groups: <70 years (n = 119), 70–79 years (n = 73), and ≥80 years (n = 24). Although there were no significant intergroup differences in preoperative characteristics and surgery-related factors except for age, patients aged ≥80 years tended to have a worse performance status (PS), Barthel index, and EuroQol-5 dimension (EQ-5D) before and after surgery than the other two groups. Although the median PS, mean Barthel index and mean EQ-5D greatly improved postoperatively in each group, the median PS and mean Barthel index at 6 months and the mean EQ-5D at 1 month postoperatively were significantly poorer in the ≥80-year group than the 70–79-year group. The rates of postoperative complications and re-deterioration of the EQ-5D were significantly higher in the oldest group than in the other two groups. Although surgery for spinal metastases improved the PS, Barthel index, and EQ-5D regardless of age, clinicians should be aware of the poorer outcomes and higher complication rates in advanced-age patients. [ABSTRACT FROM AUTHOR]

Introduction: Lungs are one of the most common sites for metastatic tumors in the body. In addition, primary lung tumors are the most common cause of death due to neoplasms in both genders. Treatment strategies are completely different for primary and metastatic lung tumors making accurate diagnosis of lung tumors an effective factor in planning the correct treatment. The development of personalized medicine and targeted therapy, especially in the treatment of primary lung tumors, has highlighted the importance of correct diagnosis of these tumors. Case report: The Pathology Center of Imam Khomeini Hospital Cancer Institute in Tehran, Iran, as a referral center for cancer across the country, is faced with a large number of lung biopsies, and therefore, there will be numerous diagnostic challenges. In this article, we presented two cases of primary female genital tract (cervical) tumors that during follow up lung masses were detected. Diagnosis on lung biopsy assigned as primary lung adenocarcinoma. Both cases referred to our lab for second opinion accompanied with related resected sample and implementation of further supplementary markers documented metastatic origin of tumors. Discussion & conclusion: In both cases, similarity in immunohistochemical characteristics of metastatic tumors with primary lung adenocarcinoma, especially positive nuclear TTF1 staining led to misdiagnosis of lung tumor origin. This finding emphasizes on the use of other specific markers related to primary site of tumor to decrease possibility of incorrect diagnosis of the origin of the tumor in metastatic setting. Due to remarkable influence of primary versus metastatic origin of lung tumor on selection of treatment, pathologists should be considered correct diagnosis and notice to similarity of immunohistochemical markers of primary lung tumors to other organs and implementation of more specific markers are necessary. [ABSTRACT FROM AUTHOR]

Oncolytic viruses (OVs) have emerged as a very promising anti-cancer therapeutic strategy in the past decades. However, despite their pre-clinical promise, many OV clinical evaluations for cancer therapy have highlighted the continued need for their improved delivery and targeting. Mesenchymal stromal cells (MSCs) have emerged as excellent candidate vehicles for the delivery of OVs due to their tumor-homing properties and low immunogenicity. MSCs can enhance OV delivery by protecting viruses from rapid clearance following administration and also by more efficiently targeting tumor sites, consequently augmenting the therapeutic potential of OVs. MSCs can function as “biological factories,” enabling OV amplification within these cells to promote tumor lysis following MSC-OV arrival at the tumor site. MSC-OVs can promote enhanced safety profiles and therapeutic effects relative to OVs alone. In this review we explore the general characteristics of MSCs as delivery tools for cancer therapeutic agents. Furthermore, we discuss the potential of OVs as immune therapeutics and highlight some of the promising applications stemming from combining MSCs to achieve enhanced delivery and anti-tumor effectiveness of OVs at different pre-clinical and clinical stages. We further provide potential pitfalls of the MSC-OV platform and the strategies under development for enhancing the efficacy of these emerging therapeutics.

Aim. To study the possibilities of bronchoscopy in the detection and evaluation of metastatic lung tumors. Materials and methods. From 2017 to September 2020, 3719 bronchoscopies, including 1081 biopsies during bronchoscopy were performed at the Blokhin National Medical Research Center of Oncology. According to the results of the morphological verification, 40 patients had been diagnosed with lung metastasis. Results. Endobronchial metastatic tumors from extrapulmonary malignancies are quite rare. After had studying 40 cases of metastatic bronchial tumors, we found that the most commonly primary malignancies associated with endobronchial metastases were breast cancer (12 patients), colorectal cancer (6 patients) and thyroid cancer (4 patients). All patients who had been diagnosed with the pathology during the bronchoscopy had been required to make a biopsy for the purpose of morphological verification. Conclusion. The value of bronchoscopy lies in the possibility not only of the detailed visual studying and detecting the tumor pathology of the bronchial tree, but also of obtaining material for morphological analysis. In this regard, the role of biopsy during bronchoscopy is extremely important. In the visual signs of tumor lesion, it is necessary to take multiple biopsies from different parts of the tumor.

This article discusses the importance of early tumor detection, particularly in liver cancer, and the role of leucine aminopeptidase (LAP) as a potential marker for liver cancer diagnosis and prognosis assessment. The article highlights the limitations of current tumor markers and the need for new markers and multi-marker approaches to improve accuracy. The authors introduce a novel near-infrared fluorescent probe, NTAP , designed for LAP detection. They describe the synthesis of the probe and evaluate its spectral properties, including the LOD was 0.0038 U/mL, and QY was 0.32 %. The kinetic properties of NTAP , such as the relationship between LAP concentration (0–0.08 U/mL), reaction time (3 min), and fluorescence excitation spectra (475 nm) and emission spectra (715 nm) are investigated. The article also discusses the stability and selectivity of the probe and its ability to detect LAP in complex samples. Cellular imaging experiments demonstrate the NATP specificity and selectivity in detecting LAP activity and its inhibition. Animal models of liver and lung metastasis are used to evaluate the probe's imaging capabilities, showing its ability to accurately locate and detect metastatic lesions. The article concludes by emphasizing the potential applications of the NTAP probe in early tumor diagnosis, treatment monitoring, and the study of tumor metastasis mechanisms. A novel near-infrared fluorescent probe, NTAP , for detecting liver-associated protease (LAP), crucial in tumor metastasis. [Display omitted] • High selectivity, real-time monitoring, and accurate imaging of LAP activity. • Dynamic fluorescence changes enable precise LAP imaging in various settings. • NTAP probe accurately detects liver and lung metastases in mouse models. • Distinguishes lung metastasis mice from normal mice. • Tool for studying metastasis mechanisms and early cancer diagnosis. [ABSTRACT FROM AUTHOR]

Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of 2 techniques of semi-hepatic alternating radiotherapy on diffuse hepatic metastasis in patients with breast cancer. Methodology: A total of 68 breast cancer patients with diffuse liver metastasis were randomly divided into Group A (semi-hepatic alternating radiotherapy) and Group B (semi-hepatic sequential radiotherapy). In Group A (semi-hepatic sequential radiotherapy), the liver was divided into the first semi-liver and second semi-liver and alternatively treated with semi-hepatic intensity-modulated radiation therapy (IMRT). The interval between the 2 instances of semi-hepatic radiotherapy was 6 h. The average radiotherapy dose to the semi-livers was both 2 Gy/fraction, once a day, 5 times per week, with a total dose of 30 Gy for 15 days. The total radiation therapy time in Group A was 15 days in Group B (semi-hepatic sequential radiotherapy), the livers were divided into the first semi-liver and second semi-liver and treated with semi-hepatic sequential IMRT, The first semi-liver was first treated in the initial stage of radiation therapy, the average radiotherapy dose to the semi-liver was 2 Gy/fraction, once a day, 5 times per week, with a total dose of 30 Gy for 15 days. The second semi-liver was treated next in the second stage of radiation therapy, the average radiotherapy dose to the semi-liver was 2 Gy/fraction, once a day, 5 times per week, with a total dose of 30 Gy for 15 days. The total radiation therapy time in group B was 30 days. Results: The objective response rate (complete response + partial response) of Group A and Group B were 50.0% and 48.5%, respectively (p =.903). The median survival time after metastasis (median survival of recurrence) of Group A and Group B was 16.7 months and 16.2 months, respectively (p =.411). The cumulative survival rates of 6 months, 1 year, 2 years, and 3 years of Group A and Group B were 90.6% (29 of 32) and 84.8% (28 of 33) (p =.478), 65.6% (21 of 32) and 60.6% (20 of 33) (p =.675), 31.2% (10 of 32) and 27.3% (9 of 33) (p =.725), and 15.6% (5 of 32) and 0 (0 of 33) (p =.018), respectively. The differences between the 2 groups showed no statistical significance in terms of cumulative survival rates in 1 year, 2 years, however, the 3-year survival rate was significantly different. The main toxic reactions were digestive tract reactions, abnormal liver functions, and myelosuppression. The incidence of I to II degree gastrointestinal reactions was 78.13% (25 of 32) in Group A and 72.73% (24 of 33) in Group B (p =.614). The incidence of I to II abnormal liver function was 53.13% (17 of 32) in Group A and 48.48% (16 of 33) in Group B (p =.708). The differences between the 2 groups showed no statistical significance. The incidence of I to II myelosuppression was 59.38% (19 of 32) in Group A and 51.52% (17 of 33) in Group B (p =.524), respectively. The differences between the 2 groups showed no statistical significance in terms of adverse effects. Conclusion: Semi-hepatic alternating IMRT was an effective palliative treatment for diffuse liver metastasis in patients with breast cancer. Semi-hepatic alternating radiotherapy showed a trend of prolonged survival time when compared with semi-hepatic sequential radiotherapy. Compared with the former, the latter showed a trend of lower incidences of side effects without any statistical differences. Moreover, the side effects from the 2 radiotherapy techniques can be controlled through appropriate management, which is worthy of further exploration and applications. [ABSTRACT FROM AUTHOR]

Aim: This retrospective study investigated bevacizumab in treating refractory brain edema in patients with brain-metastatic tumors from different sources. Methods: From January 2013 to December 2019, 83 patients with brain metastases and refractory brain edema were treated with bevacizumab. They were divided into lung cancer group and breast cancer group. The clinical data, the efficacy, and the side effects of bevacizumab were recorded. Magnetic resonance imaging was performed before and after bevacizumab treatment. The volume of tumor and brain edema were measured respectively. Results: After treatment with bevacizumab, 72 cases of refractory brain edema were significantly relieved. The edema control rate was 93.75% in the lung cancer group and 77.14% in the breast cancer group (P <.05). The brain edema volume was significantly reduced after bevacizumab treatment from 198,286.84 ± 60,564.40 to 114,677.71 ± 42,337.38mm3 (P <.01), and the edema index was reduced from 26.14 ± 7.24 to 17.18 ± 5.14 (P <.01). Hypertension was observed in 14 cases. Conclusion: Bevacizumab could significantly reduce refractory brain edema with a control rate of 86.75%. The efficacy of bevacizumab in the treatment of refractory brain edema caused by lung cancer is better than that of breast cancer. [ABSTRACT FROM AUTHOR]

Objective. To determine the incidence and identify the clinical-morphological risk factors for the development of epileptic seizures in patients with glial and metastatic brain tumors. Materials and methods. The study included 225 patients (88.6%) with glial and 29 (11.4%) with metastatic brain tumors. Results. Statistically significant differences in the incidence of epileptic seizures depending on age and histological characteristics of tumors, level of malignancy, location, involvement of the cerebral cortex, and displacement of midline structures were found. Conclusions. Epilepsy and epileptic seizures developed in 51.11% and 24.14% cases of glial and metastatic brain tumors, respectively. Risk factors for epileptic seizures were younger age (up to 57 years), histological characteristics corresponding to diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma, malignancy grades I–III, lesions to the temporal lobe, and involvement of the cerebral cortex. Factors decreasing the risk of seizures were age over 57 years, histological characteristics corresponding to glioblastoma, metastatic tumors, malignancy grade IV, subcortical location of neoplasm, lesions to the occipital cortex, involvement of the conducting tracts (commissures) in the pathological process, subtentorial tumor location, absence of lesion in the temporal and frontal lobes of the brain, involvement of both hemispheres of the brain in the pathological process, lesions of two or more lobes of the brain, and displacement of midline structures. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non-identifiable tumors as well as the future behavior of the cancerous disease. Results: The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis. [ABSTRACT FROM AUTHOR]

Background. Primary tumors of the heart are rarely detected at autopsy, especially angiosarcomas which are primary malignant one. Objective. We presented autopsy case of cardic angiosarcoma with morphologic findings. Methods. We described adult man died in emergency service of the hospital. Results. Reported case was 33 year-old-man who was died in emergency service of hospital where he was taken when he was ill after leaving home. According the prosecution documents, and the expressions of family, it was reported that he had a heart disease; his symptoms repeated 3 day ago before he died, he thought to attend the Cardiology Clinic due to his symptoms. At autopsy on macroscopic internal examination, mass with rough surface in the right atrium, hematoma at the posterior of the right atrium, blood in the pericardia, nodular lesions in hemorrhagic appearance in the sections of lung, liver and spleen were detected. In histopathologic examination; in the heart angiosarcioma as primary malign heart tumor and metastatic masses in the liver, spleen and lung were detected. Conclusions. We aimed to discuss cardiac angiosarcoma case with autopsy and histopathologic findings in the aspect of medico legal literature.

Background: The combination of radiotherapy and immunotherapy can bring benefits to patients, especially advanced patients. However, conventional radiotherapy brings about great adverse reactions. How about the hypofractionated low-dose radiotherapy? Materials and Methods: In this retrospective cohort study, we included 32 patients with metastatic solid tumors treated with hypofractionated radiotherapy combined with an immune checkpoint inhibitor. Patients underwent radiotherapy of 4Gy/Fx on day 1, 3, and 5, and received single-drug immunotherapy of PD-1 inhibitor on day 2. We evaluated the following outcomes: objective response rate (ORR), disease control rate (DCR), change of nonirradiated and irradiated lesions, quality of life, and symptom improvement. Results: Among the 32 patients, the ORR was 9.4% (3/32) and the DCR was 56.25% (18/32). Hypofractionated radiotherapy combined with immunotherapy showed a remarkable efficacy of local control on metastatic tumor patients. Local masses irradiated in two patients (6.25%) were complete remission, partial response rate was 37.5% (12 patients), and 56.25% was stability (18 patients). Out of those 18 patients, 15 patients had the local masses shrank more or less. The ORR of local control reached 43.75%, and its DCR was 100%. In addition, the intratumor necrosis rate was 44.4% in the SD patients. Median progression-free survival was 3.8 months (95%Cl: 2.2– 5.4). By treating the local mass, the symptoms of most patients were alleviated, and the quality of life was improved. Conclusion: Our retrospective analysis revealed that hypofractionated radiotherapy combined with immunotherapy was effective in local control, it also relieved clinical symptoms and improved quality of life. The adverse effect rate was low. However, the incidence of abscopal effects was low either. This mode was suitable for the palliative treatment and expected to improve survival for patients with metastatic tumors. [ABSTRACT FROM AUTHOR]

The application of nanocarriers as drug delivery system for chemotherapeutic drugs has become a research hotspot in cancer treatment. Chemotherapy with high tumor-targeting accuracy and drug release specificity is the key to improve the efficacy of tumor chemotherapy and reduce the side effects caused by repeated doses drugs. Here, we synthesized a redox-sensitive nano-micelle formed by hyaluronic acid (HA) conjugated with d -α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST), which could actively accumulate to the tumor sites and metastasis cancer cells with high expression of CD44. The micelles could dissociate under the high GSH level in cancer cells, triggering a release of paclitaxel (PTX). Surprisingly, the precise chemotherapy instead induced a suppressive tendency of immune system, manifested by a significant increase in TGF-β, which weakened the therapeutic effect of micelles. Moreover, the high levels of TGF-β might be related to the increased drug-resistance of cancer cells. Research has shown that PD-1 pathway blockade can result in reduction in TGF-β expression, thus, a PLGA microsphere encapsulating PD-1 antagonist peptides A12 (A12@PLGA) was further prepared to activate the host immune response. Our data indicated that PTX-loaded HSST could accurately "find" the tumors as well as metastasis cancer cells, and efficiently kill most of them. The joining of a durable PD-1 blockage significantly boosted the efficacy of PTX@HSST on multiple tumor models, including lung metastatic tumors and even multidrug-resistant tumors. Thus, our work presented an optimal chemo-immunotherapy combined system, which shows profound significance for future cancer therapy in clinic. Unlabelled Image • Precise targeting of drugs is the key to enhancing the effect of tumor chemotherapy • Precise chemotherapy instead suppresses the immune system • Continuous PD-1 blockade can activate the suppressed immune system [ABSTRACT FROM AUTHOR]

The current approach to systemic therapy for metastatic cancer is aimed predominantly at inducing apoptosis of cancer cells by blocking tumor-promoting signaling pathways or by eradicating cell compartments within the tumor. In contrast, a systems view of therapy primarily considers the communication protocols that exist at multiple levels within the tumor complex, and the role of key regulators of such systems. Such regulators may have far-reaching influence on tumor response to therapy and therefore patient survival. This implies that neoplasia may be considered as a cell non-autonomous disease. The multi-scale activity ranges from intra-tumor cell compartments, to the tumor, to the tumor-harboring organ to the organism. In contrast to molecularly targeted therapies, a systems approach that identifies the complex communications networks driving tumor growth offers the prospect of disrupting or “normalizing” such aberrant communicative behaviors and therefore attenuating tumor growth. Communicative reprogramming, a treatment strategy referred to as anakoinosis, requires novel therapeutic instruments, so-called master modifiers to deliver concerted tumor growth-attenuating action. The diversity of biological outcomes following pro-anakoinotic tumor therapy, such as differentiation, trans-differentiation, control of tumor-associated inflammation, etc. demonstrates that long-term tumor control may occur in multiple forms, inducing even continuous complete remission. Accordingly, pro-anakoinotic therapies dramatically extend the repertoire for achieving tumor control and may activate apoptosis pathways for controlling resistant metastatic tumor disease and hematologic neoplasia.

Aim: To evaluate the role of diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating enlarged cervical lymph nodes due to tularemia and metastatic tumors. Methods: We evaluated 59 patients with cervical lymphadenopathy (LAP) (32 patients with tularemia, 27 patients with metastatic tumors), retrospectively. We analyzed contrast enhancement patterns of LAP in postcontrast fat sat T1WI. We evaluated T2, DWI, and ADC signals of LAP in a 5-point scale system. Moreover, the mean ADC values of solid and necrotic LAP in both groups were quantitatively measured and compared statistically. Receiver operating characteristic curves of quantitative ADC values were obtained to determine the diagnostic performance. Results: There was no difference between solid and necrotic LAP enhancement patterns in two groups. Solid LAP and peripheral parts of necrotic LAP showed diffusion restriction, whereas central parts necrotic LAP had high ADC and low DWI signal in both tularemia and metastatic groups. Signal characteristics were similar in two groups. In solid LAP, there was no significant difference between ADC values in two groups. In necrotic LAP, total, central, and peripheral quantitative ADC measurements were higher in the metastatic group than in the tularemia group. Conclusions: Conventional MRI findings were not sufficient to differentiate metastatic LAP from tularemia. DW-MRI was not helpful in solid LAP; however, ADC values of metastatic necrotic LAP were significantly higher than tularemia. Microagglutination tests would be useful for differentiation; however, DW-MRI might also be useful for differentiation and may expedite the diagnosis. [ABSTRACT FROM AUTHOR]

Detecting the origin of the primary cancer that metastasizes in the oral cavity in patients with multiple primary cancers is challenging because of its rarity and complexity. We present an unusual case of an 86‐year‐old women with a maxillary gingival tumor that was histologically proven to be adenocarcinoma; she had been diagnosed with rectal and lung adenocarcinoma. A multidisciplinary approach involving complementary molecular analysis of KRAS gene mutation helped in the diagnosis of metastatic gingival tumor from rectal cancer. [ABSTRACT FROM AUTHOR]

The current approach to systemic therapy for metastatic cancer is aimed predominantly at inducing apoptosis of cancer cells by blocking tumor-promoting signaling pathways or by eradicating cell compartments within the tumor. In contrast, a systems view of therapy primarily considers the communication protocols that exist at multiple levels within the tumor complex, and the role of key regulators of such systems. Such regulators may have far-reaching influence on tumor response to therapy and therefore patient survival. This implies that neoplasia may be considered as a cell non-autonomous disease. The multi-scale activity ranges from intra-tumor cell compartments, to the tumor, to the tumor-harboring organ to the organism. In contrast to molecularly targeted therapies, a systems approach that identifies the complex communications networks driving tumor growth offers the prospect of disrupting or "normalizing" such aberrant communicative behaviors and therefore attenuating tumor growth. Communicative reprogramming, a treatment strategy referred to as anakoinosis, requires novel therapeutic instruments, so-called master modifiers to deliver concerted tumor growth-attenuating action. The diversity of biological outcomes following pro-anakoinotic tumor therapy, such as differentiation, trans-differentiation, control of tumor-associated inflammation, etc. demonstrates that long-term tumor control may occur in multiple forms, inducing even continuous complete remission. Accordingly, pro-anakoinotic therapies dramatically extend the repertoire for achieving tumor control and may activate apoptosis pathways for controlling resistant metastatic tumor disease and hematologic neoplasia. [ABSTRACT FROM AUTHOR]

Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy. [ABSTRACT FROM AUTHOR]

The progression of cancer through local expansion and metastasis is well recognized, but preventing these characteristic cancer processes is challenging. To this end, a new strategy is required. In this study, we presented a novel dual functional podophyllotoxin derivative, 2-pyridinealdehyde hydrazone dithiocarbamate S-propionate podophyllotoxin ester (PtoxPdp), which inhibited both matrix metalloproteinases and Topoisomerase II. This new podophyllotoxin derivative exhibited significant anti-proliferative, anti-metastatic that correlated with the downregulation of matrix metalloproteinase. In a xenograft animal local expansion model, PtoxPdp was superior to etoposide in tumor repression. A preliminary mechanistic study revealed that PtoxPdp induced apoptosis and autophagy via the PI3K/AKT/mTOR pathway. Furthermore, PtoxPdp could also inhibit epithelial–mesenchymal transition, which was achieved by downregulating both PI3K/AKT/mTOR and NF-κB/Snail pathways. Taken together, our results reveal that PtoxPdp is a promising antitumor drug candidate. [ABSTRACT FROM AUTHOR]

Background: Pleural fluid homocysteine (HCY) can be useful for diagnosis of malignant pleural effusion (MPE). There are no published studies comparing the diagnostic accuracy of HCY with other tumour markers in pleural fluid for diagnosis of MPE. The aim was to compare the accuracy of HCY with that of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA19.9 and CA125 in pleural fluid and to develop a probabilistic model using these biomarkers to differentiate benign (BPE) from MPE. Methods: Patients with pleural effusion were randomly included. HCY, CEA, CA15.3, CEA19.9 and CA125 were quantified in pleural fluid. Patients were classified into two groups: MPE or BPE. By applying logistic regression analysis, a multivariate probabilistic model was developed using pleural fluid biomarkers. The diagnostic accuracy was determined by receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Results: Population of study comprised 133 patients (72 males and 61 females) aged between 1 and 96 years (median = 70 years), 81 BPE and 52 MPE. The logistic regression analysis included HCY (p<0.0001) and CEA (p = 0.0022) in the probabilistic model and excluded the other tumour markers. The probabilistic model was: HCY+CEA = Probability(%) = 100×(1+e-z)-1, where Z = 0.5471×[HCY]+0.3846×[CEA]–8.2671. The AUCs were 0.606, 0.703, 0.778, 0.800, 0.846 and 0.948 for CA125, CA19.9, CEA, CA15.3, HCY and HCY+CEA, respectively. Conclusions: Pleural fluid HCY has higher accuracy for diagnosis of MPE than CEA, CA15.3, CA19.9 and CA125. The combination of HCY and CEA concentrations in pleural fluid significantly improves the diagnostic accuracy of the test. [ABSTRACT FROM AUTHOR]

Background: Personalized targeted treatment in metastatic breast cancer relies on accurate assessment of molecular aberrations, e.g. overexpression of Human Epidermal growth factor Receptor 2 (HER-2). Molecular interrogation of circulating tumor cells (CTCs) can provide an attractive alternative for real-time biomarker assessment. However, implementation of CellSearch-based HER-2 analysis has been limited. Immunofluorescent (IF) image interpretation is crucial, as different HER-2 categories have been described. Major questions in CTC research are how these IF categories reflect gene expression and amplification, and if we should consider ‘medium’ HER-2 expressing CTCs for patient selection. Methods: Tumor cells from spiked cell lines (n = 8) and CTCs (n = 116 samples) of 85 metastatic breast cancer patients were enriched using CellSearch. Comparative analysis of HER-2 expression by IF imaging (ACCEPT, DEPArray, and visual scoring) with qRT-PCR and HER-2/neu FISH was performed. Results: Automated IF HER-2-profiling by DEPArray and ACCEPT delivered comparable results. There was a 98% agreement between 17 trained observers (visual scoring) and ACCEPT considering HER-2neg and HER-2high expressing CTCs. However, 89% of HER-2med expressing CTCs by ACCEPT were scored negative by observers. HER-2high expressing tumor cells demonstrated HER-2/neu gene amplification, whereas HER-2neg and HER-2med expressing tumor cells and CTCs by ACCEPT were copy-number neutral. All patients with HER-2-positive archival tumors had ≥1 HER-2high expressing CTCs, while 80% of HER-2-negative patients did not. High relative gene expression of HER-2 measured on enriched CTC lysates correlated with having ≥1 HER-2high expressing CTCs. Conclusion: Automated images analysis has enormous potential for clinical implementation. HER-2 characterization and clinical trial design should be focused on HER-2high expressing CTCs. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) that primarily target angiogenesis are approved to treat several cancers in the metastatic setting; however, resistance is common. Sequential treatment or ‘switching’ from one TKI to another following failure can be effective, but predicting which drugs will have cross-over sensitivity remains a challenge. Here we examined sitravatinib (MGCD516), a spectrum-selective TKI able to block MET, TAM (TYRO3, AXL, MerTK) and multiple receptor families (including PDGFRs, VEGFRs, and Ephs). Transcriptomic analysis of several mouse and human cell lines revealed diverse molecular changes after resistance to two TKIs (sunitinib and axitinib) with multiple sitravatinib targets found to be upregulated. Sitravatinib treatment in vitro resulted in enhanced anti-proliferative effects in resistant cells and was improved compared to TKIs with similar target profiles. In vivo, primary tumor growth inhibition after sitravatinib treatment in mice was enhanced in resistant tumors and metastasis suppression improved when tumors were surgically removed. Together, these results suggest that the diverse and often inconsistent compensatory signaling mechanisms found to contribute to TKI resistance may paradoxically improve the tumor-inhibiting effects of broad-spectrum TKIs such as sitravatinib that are able to block multiple signaling pathways. Sitravatinib in the second-line setting following antiangiogenic TKI treatment may have enhanced inhibitory effects in local and disseminated disease, and improve outcomes in patients with refractory disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC). Methods: We performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous). Results: The overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis. Conclusion: The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) exhibits a variety of phenotypes with regard to disease progression and treatment response. This variability complicates clinical decision-making despite the improvement of survival due to the recent introduction of FOLFIRINOX (FFX) and nab-paclitaxel. Questions remain as to the timing and sequence of therapies and the role of radiotherapy for unresectable PDAC. Here we developed a computational analysis platform to investigate the dynamics of growth, metastasis and treatment response to FFX, gemcitabine (GEM), and GEM+nab-paclitaxel. Our approach was informed using data of 1,089 patients treated at the Massachusetts General Hospital and validated using an independent cohort from Osaka Medical College. Our framework establishes a logistic growth pattern of PDAC and defines the Local Advancement Index (LAI), which determines the eventual primary tumor size and predicts the number of metastases. We found that a smaller LAI leads to a larger metastatic burden. Furthermore, our analyses ascertain that i) radiotherapy after induction chemotherapy improves survival in cases receiving induction FFX or with larger LAI, ii) neoadjuvant chemotherapy improves survival in cases with resectable PDAC, and iii) temporary cessations of chemotherapies do not impact overall survival, which supports the feasibility of treatment holidays for patients with FFX-associated adverse effects. Our findings inform clinical decision-making for PDAC patients and allow for the rational design of clinical strategies using FFX, GEM, GEM+nab-paclitaxel, neoadjuvant chemotherapy, and radiation. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of CXC subfamily ligands in stage I-III patients with colorectal cancer, in order to find a new predictor for CRC patients. Methods: We used Gene Expression Omnibus (GEO) database to collect the gene expression of CXC subfamily ligands and corresponding clinical data. The survival analysis was performed by "survival" package of Rsoftware. The CRC patients’ DFS and the relationship between the expression levels of CXC subfamily ligands were evaluated by the univariate Cox regression analysis. Results: By using microarray data, there were 14 CXC subfamily ligands identified from dataset GSE39582. Seven CXC subfamily ligands were significantly correlated with DFS in CRC patients. (p<0.05),including CXCL1, CXCL3, CXCL9, CXCL10, CXCL11, CXCL13, and CXCL14. From multivariate Cox regression analyze, four CXC subfamily ligands (CXCL9, CXCL10, CXCL11, and CXCL13) were significantly associated with CRC patients’ DFS (all p<0.05). Three CXC subfamily ligands (CXCL10, CXCL11, and CXCL13) were significantly associated with CRC patients’ Overall survival (OS) (all p<0.05). Both CXCL11 and CXCL13 had the similar prediction values for DFS and OS. Conclusion: There were seven CXC subfamily ligands were significantly correlated with DFS in CRC patients. Different expression level of four CXC subfamily ligands (CXCL9, CXCL10, CXCL11, and CXCL13) and Three CXC subfamily ligands (CXCL10, CXCL11, and CXCL13) were related to CRC patients’ DFS and OS. There are still needs more experiments to confirm our conclusions. Next step we will make animal experiment about the genes in order to verified the predictive value of the CXC subfamily ligands. [ABSTRACT FROM AUTHOR]

Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. MAPK signaling, analyzed by targeted proteomics, shows unexpected heterogeneity irrespective of RAS mutations and is associated with variable responses to EGFR inhibition. In addition, we obtained evidence for intratumoral heterogeneity in drug response among parallel “sibling” 3D cultures established from a single KRAS-mutant CRC. Our results imply that separate testing of drug effects in multiple subpopulations may help to elucidate molecular correlates of tumor heterogeneity and to improve therapy response prediction in patients. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancers (CRCs) deficient in the DNA mismatch repair protein MutL homolog 1 (MLH1) display distinct clinicopathological features and require a different therapeutic approach compared to CRCs with MLH1 proficiency. However, the molecular basis of this fundamental difference remains elusive. Here, we report that MLH1-deficient CRCs exhibit reduced levels of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1), and that tumor progression and metastasis of CRCs correlate with SPTAN1 levels. Methods and results: To investigate the link between MLH1 and SPTAN1 in cancer progression, a cohort of 189 patients with CRC was analyzed by immunohistochemistry. Compared with the surrounding normal mucosa, SPTAN1 expression was reduced in MLH1-deficient CRCs, whereas MLH1-proficient CRCs showed a significant upregulation of SPTAN1. Overall, we identified a strong correlation between MLH1 status and SPTAN1 expression. When comparing TNM classification and SPTAN1 levels, we found higher SPTAN1 levels in stage I CRCs, while stages II to IV showed a gradual reduction of SPTAN1 expression. In addition, SPTAN1 expression was lower in metastatic compared with non-metastatic CRCs. Knockdown of SPTAN1 in CRC cell lines demonstrated decreased cell viability, impaired cellular mobility and reduced cell-cell contact formation, indicating that SPTAN1 plays an important role in cell growth and cell attachment. The observed weakened cell-cell contact of SPTAN1 knockdown cells might indicate that tumor cells expressing low levels of SPTAN1 detach from their primary tumor and metastasize more easily. Conclusion: Taken together, we demonstrate that MLH1 deficiency, low SPTAN1 expression, and tumor progression and metastasis are in close relation. We conclude that SPTAN1 is a candidate molecule explaining the tumor progression and metastasis of MLH1-deficient CRCs. The detailed analysis of SPTAN1 is now mandatory to substantiate its relevance and its potential value as a candidate protein for targeted therapy, and as a predictive marker of cancer aggressiveness. [ABSTRACT FROM AUTHOR]

The article offers information on the analysis of prostate cancer in terms of mutated genes. It mentions result of analysis that found mutated genes follows a long tail, with genes containing a substitution in comparatively many tumors, and many genes containing a substitution in few tumors. It also mentions ranking genes discovered by the prevalence of the mutations that are observed at high frequencies.