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The Journal of Organic Chemistry Jul 2023Alkyl thiocyanurates, the compounds formed in the SN reaction of thiocyanuric acid and alkyl halides, are susceptible to transthioesterification and ligation with...
Alkyl thiocyanurates, the compounds formed in the SN reaction of thiocyanuric acid and alkyl halides, are susceptible to transthioesterification and ligation with molecules containing cysteamine, analogous to native chemical ligation of thioesters with peptides with an N-terminal cysteine moiety. The ligation is irreversible and results in the formation of mono- and disubstituted products dominantly. Transthioesterification, in contrast, is fully reversible and may be used in constructing dynamic systems. The application of this reactivity in dynamic covalent chemistry has been exemplified by the preparation of a library of mixed thiocyanurates of glutathione and thioglycolic acid with self-assembly abilities and metathesis between thiocyanurates of tris(carboxymethyl) and tris(carboxamidomethyl) catalyzed by MESNa (sodium 2-mercaptoethylsulphonate) or MPAA (4-mercaptophenylacetic acid). Differences in reactivity of thiocyanurates toward cysteamines and thiols has been explained based on conceptual DFT.
Topics: Peptides; Sulfhydryl Compounds; Cysteine; Mesna; Glutathione
PubMed: 37329497
DOI: 10.1021/acs.joc.3c00200 -
Cureus Apr 2023Primary mesenteric liposarcoma is a rare soft tissue malignant neoplasm. The authors present a case of a 42-year-old male with pain in the abdomen and abdominal mass...
Primary mesenteric liposarcoma is a rare soft tissue malignant neoplasm. The authors present a case of a 42-year-old male with pain in the abdomen and abdominal mass which showed a desmoid tumor on biopsy and CT shows a mesenteric mass present. The patient underwent exploratory laparotomy and a large tumor was excised. The specimen was sent for histopathology and showed dedifferentiated liposarcoma of the mesentery. Immunohistochemistry showed the tumor cells are diffusely positive for mouse double minute 2 (MDM2), p16, and show patchy positivity for the cluster of differentiation (CD) 34. The cells are negative for smooth muscle actin (SMA), desmin, S100, and ckit. After the surgery, the patient recovered well and was given adjuvant chemotherapy with doxorubicin, ifosfamide, and mesna. The patient has no signs or symptoms of recurrence to date. In this case, the combination of surgery and chemotherapy has shown to have a good clinical outcome.
PubMed: 37261141
DOI: 10.7759/cureus.38329 -
Cureus Jan 2023Posterior reversible encephalopathy syndrome (PRES) is a syndrome encompassing both clinical and radiological manifestations with white matter vasogenic edema...
Posterior reversible encephalopathy syndrome (PRES) is a syndrome encompassing both clinical and radiological manifestations with white matter vasogenic edema predominantly of the posterior and parietal lobes of the brain. It may accompany several medical conditions including immunosuppressive/cytotoxic drugs. We present a case of cyclophosphamide-induced PRES in a patient treated for acute lupus flare with biopsy-proven lupus nephritis. A 23-year-old African American female presented with non-specific symptoms over a six-month period on a medical background of systemic lupus erythematosus and biopsy-proven focal lupus nephritis class III on hydroxychloroquine, prednisone, and mycophenolate mofetil for which she was non-compliant. She was borderline hypertensive, tachycardic, saturating well on ambient air, and alert and oriented. Laboratory workup revealed electrolyte imbalance, elevated serum urea, creatinine, and B-type natriuretic peptide, low serum complements, and elevated double-stranded DNA (dsDNA) with negative lupus anticoagulant, anti-cardiolipin, and B2 glycoprotein antibody. Chest imaging revealed cardiomegaly with small pericardial effusion, left pleural effusion, and trace atelectasis, with no deep vein thrombosis on Doppler ultrasound. She was admitted to the intensive care unit for lupus flare with severe hyponatremia and was continued on mycophenolate mofetil, hydroxychloroquine, and prednisone 60 mg for induction therapy as well as intravenous fluids. Hyponatremia resolved, and blood pressure was controlled. She became fluid overloaded and anuric, with pulmonary edema and worsening hypoxic respiratory failure not responding to diuretic challenges. Daily hemodialysis was started, and she was intubated. Prednisone was tapered down, mycophenolate was switched to cyclophosphamide/mesna. She became agitated, restless, and confused, with waxing and waning consciousness and hallucinations. She was continued on bi-weekly cyclophosphamide for induction therapy. After the second dose of cyclophosphamide, her mentation worsened. Non-contrast MRI showed extensive bilateral cerebral and cerebella deep white matter high-intensity signals suggestive of PRES, which was new compared to one year prior. Cyclophosphamide was held and her mentation improved. She was successfully extubated and discharged to a rehabilitation center. The exact pathophysiological mechanism of PRES is not known. Endothelial damage and vasogenic edema have been hypothesized as possible mechanisms. Severe anemia, fluid overload, and renal failure are some of the causes of endothelial dysfunction and vasogenic edema with disruption of the blood-brain barrier, which were found in our patient, but repeated dosing of cyclophosphamide worsened her condition. Discontinuation of cyclophosphamide led to a significant improvement and complete reversal of her neurologic symptoms, implying that prompt recognition and management of PRES is vital to prevent permanent damage and even death in these patients.
PubMed: 36874730
DOI: 10.7759/cureus.34372 -
Frontiers in Oncology 2022Retroperitoneal liposarcoma (RPLS) is a rare malignancy that is notorious for recurrence. Surgical resection with clean margin is the current treatment of choice....
BACKGROUND
Retroperitoneal liposarcoma (RPLS) is a rare malignancy that is notorious for recurrence. Surgical resection with clean margin is the current treatment of choice. However, owing to the large retroperitoneal space, RPLSs often grow to significant sizes before being diagnosed. Neoadjuvant and adjuvant therapies have potentials to improve long term treatment outcome.
CASE PRESENTATION
A 55-year-old Han Chinese male presented to the general surgery department with a one-year history of abdominal fullness and a one-week history of palpable right inguinal mass. At first, he was diagnosed with incarcerated inguinal hernia. However, abdominal computer tomography (CT) and biopsy confirmed his final diagnosis to be retroperitoneal well-differentiated liposarcoma, cT2bN0M0, stage IIb. The tumor, which measured 44.5cm in maximum diameter, was too large for primary surgical resection. Neoadjuvant radiotherapy with 70 Gy in 35 fractions was delivered to the tumor, which shrunk the target volume from 6300 cc to 4800 cc, as observed in the middle of the radiotherapy course. The right testicular mass also received 70Gy/35Fx. Conversion surgery was performed after radiotherapy. Unfortunately, due to residual tumor, adjuvant chemotherapy consisting of AIM (ifosfamide, Mesna, and doxorubicin) and MAID (Mesna, doxorubincin, ifosfamide, and dacarbazine) regimens were administered sequentially. Afterward, debulking surgery was conducted, plus another 18 cycles of ifosfamide monotherapy when residual tumor was still seen on CT. Since the completion of ifosfamide chemotherapy, the patient has been cancer free with no evidence of tumor recurrence for more than 26 months.
CONCLUSION
Despite conflicting evidence in the literature, our case supports the use of high dose neoadjuvant radiotherapy and adjuvant chemotherapy in treating large, unresectable RPLSs. It also highlights the importance of using individualized, multidisciplinary approach in achieving cure for large, unresectable rare tumors.
PubMed: 36686723
DOI: 10.3389/fonc.2022.1096411 -
Cureus Nov 2022Malignant peripheral nerve sheath tumors (MPNST) are a rare form of sarcoma derived from Schwann cells. Major risk factors for development are neurofibromatosis 1 (NF1)...
Malignant peripheral nerve sheath tumors (MPNST) are a rare form of sarcoma derived from Schwann cells. Major risk factors for development are neurofibromatosis 1 (NF1) and prior radiation exposure. Tumor location is highly variable. We present a case of an extremely large MPNST tumor in the anterior mediastinum in a 66-year-old male. To the best of our knowledge, the 20.5 cm tumor is the first of its kind in a patient without clinical signs of NF1 or prior radiation exposure. The localization of this tumor to the anterior mediastinum is rarer, as the most common tumors presenting in this area are thyroid neoplasms, thymomas, teratomas, and lymphomas. The patient's tumor responded to doxorubicin-ifosfamide-mesna-based therapy. The tumor decreased from 20.5 cm to 9.0 cm on subsequent imaging. Thus, this is an interesting and valuable case to learn about the presentation and potential treatments of such a rare pathology.
PubMed: 36514670
DOI: 10.7759/cureus.31299 -
Frontiers in Oncology 2022Hepatic undifferentiated embryonal sarcoma of the liver (UESL) is a rare hepatic malignancy found more commonly in pediatric patients. It has been associated with poor...
Hepatic undifferentiated embryonal sarcoma of the liver (UESL) is a rare hepatic malignancy found more commonly in pediatric patients. It has been associated with poor outcomes in adults and the role and timing of systemic therapy is unclear. There have been very few case reports detailing combination neoadjuvant and adjuvant chemotherapy use for hepatic undifferentiated embryonal sarcoma in adults. In this report, a 22-year-old male admitted with right upper quadrant pain was diagnosed with a 20 x 10 x 10 cm well-circumscribed, highly vascularized hepatic mass in the entirety of the left lobe. Biopsy confirmed the diagnosis of UESL. PET/CT showed no evidence of metastatic disease, and he received four cycles of Doxorubicin and Ifosfamide with demonstrated reduction in size and decrease in PET avidity. He underwent left hepatectomy with periportal lymphadenectomy, cholecystectomy, and partial gastrectomy with negative margins and received adjuvant Doxorubicin, Ifosfamide and Mesna. At 48 months, the patient was alive without evidence of disease. We hereby emphasize the potential advantages of combination chemotherapy and surgical resection in the management of UESL in adults.
PubMed: 36465387
DOI: 10.3389/fonc.2022.1004108 -
Annals of Medicine and Surgery (2012) Nov 2022Spine surgery and spinal fusion surgery are rising. Revision rates following initial surgery are between 8 and 45%. Epidural fibrosis is a common response to spine...
UNLABELLED
Spine surgery and spinal fusion surgery are rising. Revision rates following initial surgery are between 8 and 45%. Epidural fibrosis is a common response to spine surgery for most patients and increases complications in revision surgery. Previous research suggests using MESNA (Sodium 2-mercaptoethane sulfonate) in combination with mechanical blunt dissection safely reduces surgical complications. MESNA is a mucolytic agent which selectively cleaves disulphide bonds involved in the adherence and strength of fibrosis, meaning cutting instruments are not needed. The Chemically Assisted DISSection (CADISS®) System is an optimised non-cutting surgical device, consisting of a reconstitution cartridge for MESNA preparation, irrigated surgical instruments, and a footswitch to control MESNA release. This is the first study to investigate the use of the CADISS® System in revision spine surgery.
METHODS
This was a prospective, open label, observational case study. We enrolled 21 patients for revision spine surgery with the CADISS® System at two Belgium sites. The primary assessment was the number of successful removals of epidural fibrosis without cutting. The amount of MESNA used, total dissection and procedure time were recorded. For secondary criterion, the surgeons assessed global satisfaction, facilitation of dissection, quickness of action, usability, bleeding reduction and visualisation of the cleavage plane using an 11-point Likert scale (0-10). Due to the exploratory nature, no formal statistical analysis was planned. We calculated the percentage and confidence interval of successful procedures, the medians and corresponding interquartile range of the Likert criterion, and the mean (±SD) of the amount of MESNA used, CADISS® dissection time and total procedure time.
RESULTS
24 fibrosis dissections were performed in 19 patients and 23 were successful (95.8%, CI: 78.9%; 99.9%). The mean amount of MESNA used, mean dissection time and procedure time were 16 ml (±4.94), 16.5 min (±16.1) and 86.3 min (±25.1), respectively. No dural tears were reported. The mean global satisfaction score was 9.0 (8.0-9.0). All other Likert criterion had scores of 8.0 or 9.0, excluding quickness of action, which scored 7.0 (6.0-9.0).
CONCLUSIONS
The CADISS® System in revision spine surgery has potential to effectively reduce dissection complications.
PubMed: 36389182
DOI: 10.1016/j.amsu.2022.104718 -
Communications Biology Oct 2022Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane...
Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane metabolism, catalyzing the last step in methanogenesis and the first step in anaerobic methane oxidation. Divergent mcr and mcr-like genes have recently been identified in uncultured archaeal lineages. However, the assembly and biochemistry of MCRs from uncultured archaea remain largely unknown. Here we present an approach to study MCRs from uncultured archaea by heterologous expression in a methanogen, Methanococcus maripaludis. Promoter, operon structure, and temperature were important determinants for MCR production. Both recombinant methanococcal and ANME-2 MCR assembled with the host MCR forming hybrid complexes, whereas tested ANME-1 MCR and ethyl-coenzyme M reductase only formed homogenous complexes. Together with structural modeling, this suggests that ANME-2 and methanogen MCRs are structurally similar and their reaction directions are likely regulated by thermodynamics rather than intrinsic structural differences.
Topics: Archaea; Mesna; Oxidoreductases; Methane
PubMed: 36266535
DOI: 10.1038/s42003-022-04057-6 -
Cancer Reports (Hoboken, N.J.) Nov 2022Ewing sarcoma (ES), the second most common malignant bone tumor after osteosarcoma in the second decade, occurs in 0.9% of cases as the primary non-sacral form.
BACKGROUND
Ewing sarcoma (ES), the second most common malignant bone tumor after osteosarcoma in the second decade, occurs in 0.9% of cases as the primary non-sacral form.
CASE
A 20-years-old male presented with acute paraparesis of bilateral lower limb and numbness following initial back pain for the last 6 months. Magnetic resonance imaging (MRI) of the lumbar spine revealed a 4 cm enhancing soft tissue mass at the L4/L5 vertebra extending into the spinal canal with compression of the thecal sac. The computed tomography (CT) of the chest, abdomen, and pelvis revealed aggressive lytic lesions in the L4 spinous process with soft tissue extension into the spinal canal with no other site of distant metastasis. He was treated with IV steroids (Injection dexamethasone 10 mg IV followed by 4 mg tablet dexamethasone q6h; subsequently tapered off). A core needle biopsy showed a small, round blue cell neoplasm, (suggestive of a primitive neuroectodermal) stained positive for CD99 and vimentin stain. The diagnosis of ES lumbar spine was made which was treated with surgical resection with an appropriate margin measuring 8 × 4.5 × 2.5 cm with decompression and L4/5 laminectomies, which had a negative margin in the surgical pathology report. Concomitant local radiotherapy and chemotherapy [cycles of vincristine 2 mg/m , adriamycin/doxorubicin 75 mg/m , cyclophosphamide 1200 mg/m (VDC) with mesna rescue alternating with cycles of ifosfamide 1800 mg/m and etoposide 100 mg/m (IE)] was started. The motor strength was regained gradually with preserved spine biomechanics and oncological control with no recurrence in 2-year follow-ups.
CONCLUSIONS
The presentation of lumbar ES can vary from local pain and swelling to acute paraparesis. Timely diagnosis and treatment with multimodal therapy, namely, steroids for acute spinal cord compression and surgery with chemoradiotherapy for ES can improve spinal biomechanics and oncological control.
Topics: Humans; Male; Young Adult; Adult; Sarcoma, Ewing; Bone Neoplasms; Neoplasms, Second Primary; Spine; Paraparesis; Dexamethasone
PubMed: 36193025
DOI: 10.1002/cnr2.1725